bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–10–25
58 papers selected by
Luca Bolliger, lxBio
  1. Bacteriophage Therapy in Cystic Fibrosis: Emerging Strategies for Managing Chronic Pseudomonas aeruginosa Infections.
  2. Beyond Antibiotics: Bacteriophage Therapy Against Multidrug-Resistant Pathogens in the Era of Antimicrobial Resistance.
  3. Pathological microbial niches in diabetic foot ulcers: a host-microbe framework for impaired repair and niche-based stratification.
  4. Bacteriophage Therapy in Cardiovascular Medicine: A Paradigm Shift in the Prevention of Device-Related Infections.
  5. Phage Therapy as a Self-Replicating Strategy for Besieged Health Systems.
  6. Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections.
  7. Dosing and delivery of bacteriophage therapy in a murine wound infection model.
  8. Nursing care of a child with cerebral palsy and multidrug-resistant bacterial pneumonia treated with bacteriophage therapy: a case report.
  9. Isolation and genomic characterization of a novel Pseudomonas jumbo phage ΦBRkr.
  10. Mechanisms and Application of Bacteriophages in Regulating Intestinal Health of Livestock and Poultry.
  11. The Bidirectional Relationship Between Rheumatoid Arthritis and Periodontitis: Current Evidence and Clinical Implications.
  12. Beyond Antibacterial Activity: Engineering Multifunctional Biomaterials for Multidrug-Resistant Infections.
  13. Bacterial Defense and Phage Counterdefense: Unraveling the Molecular Basis of Phage Resistance.
  14. Salmonella phage characterization and host-dependent responses relevant to cocktail formulation.
  15. Application of bacteriophages in the prevention of Bacillus cereus infection in potatoes.
  16. Microbiota-constrained bacterial density limits phage infection in the gut and allows persistence of susceptible cells.
  17. Integrated Genomic Phenotypic and Host-response Analysis of Multidrug-resistant Diabetic Foot Infections: A Tertiary Center Study from Kerala India.
  18. The microbiome bone axis in osteomyelitis: integrating evidence from bone oral and gut microbiota.
  19. High-Throughput Spot Assay for Isolation of Bacteriophages Against Multiple Host Strains from Environmental Samples.
  20. Formulation, physicochemical characterization, and antimicrobial evaluation of drug-loaded essential oil microemulsions against Methicillin-resistant Staphylococcus aureus -associated diabetic foot ulcer infections.
  21. Invasive guests: the role of non-oral bacteria in oral dysbiosis and systemic health.
  22. Emerging Molecular Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens: A Comprehensive Review.
  23. Impact of the urinary microbiome on urinary tract infection progression.
  24. Molecular epidemiology of carbapenemase-producing gram-negative bacilli in diabetic foot infections: association with glycemic control.
  25. Continuity of Chronic Wound Care Across Hospital-to-Home Transitions: A Qualitative Study of Hospital and Community Nurses' Experiences.
  26. Biofilm-associated genes in Staphylococcus aureus: role in chronic infections and therapeutic challenges.
  27. Periodontal diseases and coronary artery disease: epidemiological links, pathogenic mechanisms and prospects for comorbidity integrated management.
  28. Cell-free Engineering of LPST153 Bacteriophage Receptor-Binding Proteins Enables Tunable Host-Range Modulation.
  29. Stable coexistence and transport of lytic phage infections with migrating bacterial hosts.
  30. The forgotten organ: Why the oral microbiome belongs in every physician's toolkit.
  31. The use of technology to improve wound care practice.
  32. Microbiome Continuum: Connecting Environmental, Host-Associated and Engineered Microbiomes Through One Health and Artificial Intelligence.
  33. Diverging mortality pathways for chronic wounds: A 26-year analysis of United States national data, 1999-2024.
  34. Management Strategies and Clinical Outcomes of Methicillin Resistant Staphylococcus Aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-Analysis.
  35. Comparative purification of a Salmonella bacteriophage for protein profiling.
  36. Live biotherapeutics in the post-antibiotic era: exploring the potential of probiotics to counter multidrug resistance.
  37. From Hypoxia to Healing: Topical Deferoxamine Enhances Wound Closure and Neovascularization in Diabetic Animal Models - A Systematic Review and Meta-Analysis.
  38. A phage-based luminescent reporter platform for rapid typing of multiple capsular types of Klebsiella pneumoniae.
  39. Wound Position is Associated with Morphological Stability and Quantitative Accuracy in Murine Skin Healing Models.
  40. Non-eligibility for highly effective modulator therapy with elexacaftor/tezacaftor/ivacaftor in cystic fibrosis: What about Portugal?
  41. Navigating Treatment Pathways in Diabetic Foot Infection: A Practical Retrospective Analysis of Healing Predictors and the WIfI System.
  42. Parvimonas micra and central nervous system infections: mechanisms of transformation from oral commensal to intracranial pathogen and clinical evidence.
  43. Unlocking the PirAB Pandora's box: Genomic epidemiology and phage biocontrol of an emerging waterborne one health crisis.
  44. From discovery to preparedness: reframing antimicrobial resistance as a global governance challenge.
  45. Fusobacterium nucleatum: a keystone bridging pathogen in polymicrobial biofilms and host immune dysregulation.
  46. Molecular control of bacterial immunity.
  47. Draft genome sequences for six Staphylococcus aureus isolates from cystic fibrosis patients in Oklahoma.
  48. Beyond the Silent Endometrium: Dysbiosis, Immune Subversion and Antimicrobial Resistance in Chronic Endometritis: A Narrative Review.
  49. Repeat antimicrobial susceptibility testing of serial bacterial isolates: clinical utility and diagnostic stewardship.
  50. Establishing a regulatory framework for phage therapy in China.
  51. Targeting the gut-liver axis and gut microbiome in pediatric metabolic dysfunction-associated steatotic liver disease: current evidence and future directions.
  52. When Clinical Prediction Models Meet Clinical Judgment: A Framework for Classifying Prediction Approaches.
  53. Electrical impedance tomography in neonatal respiratory diseases: a clinical review of applications and evidence.
  54. Global gram-negative diabetic foot infection prevalence and its associations with climate: a systematic review and meta-analysis.
  55. Artificial intelligence in pharmacy and pharmaceutical sciences: Research output, trends, and thematic priorities - A descriptive analysis of web of science-indexed publications (2010-2025).
  56. Multimodal Deep Learning for Wound Healing Prediction.
  57. Harnessing hydrogel technology for advanced periodontitis therapy: A multifunctional approach to oral health restoration.
  58. Biofilm-host immunometabolic crosstalk in Staphylococcus aureus orthopedic implant infection: mechanisms and translational constraints.
  1. Drug Des Devel Ther. 2026 ;20 612130
    Bacteriophage Therapy in Cystic Fibrosis: Emerging Strategies for Managing Chronic Pseudomonas aeruginosa Infections.
    Ayona Puthenpurayil, Lauren Gordon, Joanne L Fothergill.
      Pseudomonas aeruginosa is the leading cause of chronic respiratory infection in people with cystic fibrosis (pwCF) and remains a major driver of morbidity and premature mortality. The unique environment of the CF lung promotes persistent colonisation, biofilm formation, and the emergence of multidrug-resistant (MDR) phenotypes, severely limiting the effectiveness of conventional antibiotic therapies. Despite aggressive and prolonged antibiotic regimens, eradication of chronic P. aeruginosa infection is rarely achieved, and repeated exposure accelerates resistance development. Consequently, there is an urgent need for alternative or adjunctive therapeutic strategies. Bacteriophage (phage) therapy has re-emerged as a promising approach for treating MDR P. aeruginosa infections due to its strain specificity, self-amplifying activity, and capacity to disrupt biofilms. Importantly, phage-driven selection pressure can impose fitness costs on bacteria, including reduced virulence and increased susceptibility to antibiotics, providing a potential route to antimicrobial resensitisation. However, translating phage therapy into routine clinical practice faces challenges, particularly in the context of CF lung disease, where heterogeneous bacterial populations, thick mucus, biofilms, and host immune responses complicate treatment efficacy. This scoping review synthesises current understanding of P. aeruginosa pathogenesis in CF, focusing on antibiotic resistance mechanisms, virulence factors that function as phage receptors, and the evolutionary trade-offs exploited by phage therapy, including the role of phage-encoded depolymerases that degrade protective biofilms and bacterial defence mechanisms that drive phage resistance. We critically evaluate clinical evidence supporting phage use in pwCF, highlighting key limitations in existing studies, and priorities for future research required to establish phage therapy as a viable, regulated treatment option.
    Keywords:  Pseudomonas aeruginosa; antibiotic resistance; bacteriophage; cystic fibrosis; receptors
    DOI:  https://doi.org/10.2147/DDDT.S612130
  2. Cureus. 2026 Sep;18(9): e116535
    Beyond Antibiotics: Bacteriophage Therapy Against Multidrug-Resistant Pathogens in the Era of Antimicrobial Resistance.
    Benny Vijayanandh Avanigadda, Raja Krishna Venigalla, Renusri Ede, Pranathi Reddy Jetti, Venkataramana Kandi, Tarun Kumar Suvvari.
      The escalating global health crisis of antimicrobial resistance (AMR) urgently calls for interventions that transcend the limitations of conventional antibiotics. Bacteriophages (phage therapy) is emerging as a critical therapeutic and prophylactic agent with a distinct operational role against multidrug-resistant (MDR) pathogens. The core of the phage's utility lies in three strategic advantages: high specificity, self-amplification at the site of infection, and most crucially, their unique capacity for biofilm eradication. Since up to 80% of chronic infections involve biofilms that shield bacteria from antibiotics, the ability of phages to penetrate and disperse these structures makes them invaluable against recalcitrant infections. Phages are thus positioned not merely as an alternative, but as a strategic and complementary tool alongside antibiotics, often demonstrating synergy that can resensitize resistant bacteria to previously ineffective drugs. Overcoming current regulatory and manufacturing challenges is essential to unlock the full potential of phage therapy and secure its vital role in the global fight against AMR.
    Keywords:  amr; antimicrobial resistance; bacteriophages; multi-drug resistance; phage therapy; phages
    DOI:  https://doi.org/10.7759/cureus.116535
  3. Front Cell Infect Microbiol. 2026 ;16 1926191
    Pathological microbial niches in diabetic foot ulcers: a host-microbe framework for impaired repair and niche-based stratification.
    Min Leng, Zairong Wei.
      Diabetic foot ulcers (DFUs) are commonly described through the clinical triad of hyperglycaemia, ischaemia and infection. That language is useful for bedside decision-making, but it does not fully explain why some wounds remain inflamed and open despite debridement, offloading, antimicrobial therapy, vascular assessment and modern wound care. Here we develop a conceptual review framework in which many non-healing DFUs are interpreted as pathological microbial niches: local tissue regions where microbial persistence and host repair failure reinforce each other. Hyperglycaemia, impaired perfusion, hypoxia, neuropathic pressure injury, necrotic material and extracellular matrix degradation generate ecological space for microbial survival. Microbial products, biofilm-like spatial organisation, strain-level traits, fungi and polymicrobial interactions then amplify neutrophil extracellular traps, inflammasome signalling, protease release, fibroblast dysfunction, endothelial impairment and defective re-epithelialisation. The result is not a linear sequence from colonisation to infection to inflammation, but a self-reinforcing loop in which microbial adaptation and host non-healing programs become difficult to separate. We summarise evidence from chronic wound microbiome studies, biofilm histology, strain-level and fungal analyses, host transcriptomics, single-cell data and emerging spatial omics, while emphasising the boundaries of each evidence type. The central question is not whether microbes can be detected in DFU tissue, but whether they are viable, metabolically active, spatially organised and positioned close enough to host cells to alter repair behaviour. We propose an operational definition of the pathological microbial niche and a translational scheme for biofilm-dominant, ischaemia-dominant, protease-dominant, senescence-dominant and immune-resolution-failure wound patterns. This framing may help move DFU microbiome research from descriptive association toward mechanism-based stratification and more rational combinations of source control, vascular optimisation, antimicrobial therapy and repair-directed treatment.
    Keywords:  biofilm; diabetic foot ulcer; host-microbe interaction; multi-omics; non-healing inflammation; pathological niche; spatial omics; wound microbiome
    DOI:  https://doi.org/10.3389/fcimb.2026.1926191
  4. ACS Infect Dis. 2026 Oct 09. 12(10): 3309-3321
    Bacteriophage Therapy in Cardiovascular Medicine: A Paradigm Shift in the Prevention of Device-Related Infections.
    Abeer Alfadhli, Shankave Sritharan, Diya Rangrej, Jeffrey Ian Weitz, Zeinab Hosseinidoust, Tohid F Didar.
      Cardiovascular implant infections significantly impact morbidity and mortality. Bacteriophage therapy has emerged as a potential strategy for device-related infection, particularly in biofilm-associated settings where conventional antimicrobial therapy is limited, often necessitating device removal. This review outlines phage treatment principles, including biofilm invasion, phage-antibiotic interaction, phage resistance, and infection protection mechanisms. We explore innovative approaches for using bacteriophages to treat infections around prosthetic vascular grafts, heart valves, left ventricular assist devices, and cardiac implantable electronic devices. Key issues in using bacteriophages for cardiovascular device infections include phage selection, resistance detection, phage production, regulatory aspects, and experimental models considering infection and device flow dynamics. Although clinical trials on phage therapy effectiveness are unavailable, its promise is significant.
    Keywords:  antibiotic resistance; bacteriophage therapy; biofilm; cardiovascular device infection; vascular graft infection
    DOI:  https://doi.org/10.1021/acsinfecdis.6c00563
  5. Infect Drug Resist. 2026 ;19 638488
    Phage Therapy as a Self-Replicating Strategy for Besieged Health Systems.
    Emmanuel Olalere, Sidra Saif, Warda Imran, Faiza Khalid, Dadullah Faiz, Javeria Akhter, Laiba Manzoor, Ashesh Das.
       Background: Active conflict zones and resource-limited health settings face compounding challenges from disrupted antibiotic supply chains concurrent with the proliferation of multidrug-resistant (MDR) and pan-drug-resistant (PDR) pathogens. In such settings, drug availability directly determines clinical outcomes.
    Methods: A narrative review of the literature was conducted in accordance with adapted SANRA (Scale for the Assessment of Narrative Review Articles) criteria, searching PubMed/MEDLINE, EMBASE, Cochrane Library, and grey literature sources for articles published between 1st January 2001 and 1st April 2026. Of 8003 records identified, 42 met inclusion criteria and were incorporated into this review Seminal pre-2001 works and non-English-language sources from Eastern European phage therapy programmes were deliberately included to mitigate geographic publication bias.
    Main Findings: Bacteriophages possess unique pharmacokinetic properties, including self-replication exclusively at infection sites, enabling pathogen clearance from a minimal dose burden. The Phage Support Ukraine (PhageSP UKR) initiative demonstrated rapid local phage isolation against circulating MDR and PDR Klebsiella pneumoniae strains from combat casualties, bypassing conventional pharmaceutical manufacturing chains. In a subset of strains, phage-driven evolutionary tradeoffs can compel ESKAPE pathogensto shed resistance plasmids, including NDM-1metallo-β-lactamase determinants, re-sensitizing the effected strains to existing antibiotics - a strain-specific phenomenon rather than a general clinical outcome These effects act synergistically with host immune defences. Decades of data from the Eliava Institute and growing compassionate use evidence provide a foundational safety profile. The PhagoBurn randomised trial found bacterial burden reduction to be significantly slower with phage therapy than standard of care, a result attributable to subtherapeutic dosing in a substantial proportion of participants; it does not establish efficacy but highlights dose-optimisation as a critical unmet need prior to wider deployment.
    Conclusion: Bacteriophage therapy represents a biologically rational and logistically feasible intervention for health systems under siege. While large-scale randomised controlled trial evidence remains limited, pragmatic deployment supported by compassionate use data and adaptive regulatory frameworks provides justification for clinical application against otherwise untreatable infections in conflict and resource-limited settings. Targeted investments in phage biobanking, rapid point-of-care production protocols, and harmonized international regulatory pathways are urgently needed.
    Keywords:  antimicrobial resistance; bacteriophage; conflict medicine; eskape pathogens; multidrug resistance; phage therapy; resource-limited settings; trauma infections
    DOI:  https://doi.org/10.2147/IDR.S638488
  6. Hlife. 2025 Jun;3(6): 275-283
    Personalized bacteriophage therapy for chronic biliary tract Pseudomonas aeruginosa infections.
    Na Li, Linlin Li, Bo He, Dandan Li, Wenting Jin, Yuan Wu, Beidi Zhu, Mengjun Cheng, Nannan Wu, Demeng Tan, Jue Pan, Chunmei Zhou, Rong Bao, Hao Wu, Wen Zhang, Ming Li, Zhuojun Zhong, Jiazhen Liu, Jianglin Liao, Tongyu Zhu, Bijie Hu, Shuai Le.
      Biliary tract infections (BTIs) present a significant therapeutic challenge, particularly in the face of increasing antimicrobial resistance. Bacteriophages, viruses that target and destroy bacteria, offer the potential for treating severe bacterial infections, although their use in BTIs has been limited. We describe an 88-year-old female with a complex and recurrent BTI caused by multiple bacteria, including multidrug-resistant Pseudomonas aeruginosa. Despite treatment with various antibiotics and percutaneous transhepatic cholangiodrainage (PTCD), her condition did not improve. As a final measure, we implemented personalized phage therapy in combination with antibiotics. An initial 9-day antibiotic treatment combined with a P. aeruginosa phage cocktail administered via PTCD fluid resulted in significant symptom relief. However, phage-resistant pathogens emerged, exhibiting resistance to all 100 double-stranded DNA (dsDNA) phages in our library due to genetic mutations affecting lipopolysaccharides biosynthesis. A second round of therapy with a double-stranded RNA (dsRNA) phage, phiYY, which targets O-antigen deficient mutants, was subsequently administered. Although complete eradication of P. aeruginosa was not achieved, the patient's clinical symptoms were markedly improved. This case demonstrated the safety and efficacy of phage therapy in the treatment of BTIs and showcased the feasibility of employing dsRNA phages to combat the emergence of O-antigen-deficient bacterial mutants. However, it also underscores the considerable challenges in completely eradicating persistent P. aeruginosa infections, which may be attributed to bacterial heterogeneity, biofilm formation, and phage-resistant genetic mutations.
    Keywords:  Pseudomonas aeruginosa; biliary tract infections; phage therapy
    DOI:  https://doi.org/10.1016/j.hlife.2025.03.004
  7. Nat Commun. 2026 09 19. pii: 10984. [Epub ahead of print]17(1):
    Dosing and delivery of bacteriophage therapy in a murine wound infection model.
    Yung-Hao Lin, Tejas Dharmaraj, Qingquan Chen, Arne Echterhof, Robert Manasherob, Lucy J Zhang, Zhiwei Li, Cas de Leeuw, Nana A Peterson, Tony H W Chang, Whitney Stannard, Maryam Hajfathalian, Aviv Hargil, Hunter A Martinez, Julie Pourtois, Maya Abhyankar, Francis G Blankenberg, Derek Amanatullah, Ovijit Chaudhuri, Paul L Bollyky.
      Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, dosing and delivery strategies for phage therapy remain underdeveloped. In a mouse wound infection model specifically designed to evaluate the treatment of established infections-a critical gap in existing preclinical models-we investigated the impact of administration route, dose, and frequency on phage therapy efficacy. In this model, topical, but not systemic, delivery reduced wound bacterial burden. In vitro and in vivo data revealed rapid emergence of phage resistance and suggested potential benefit of using high and repeated doses. Building on these insights, we developed HydroPhage, a phage-containing hyaluronan-based hydrogel formed with dynamic covalent crosslinks that delivers high-titer phages over one week. Here, we show that sustained hydrogel-based delivery is a practical and effective approach for topical phage application.
    DOI:  https://doi.org/10.1038/s41467-026-77992-1
  8. Front Pediatr. 2026 ;14 1955901
    Nursing care of a child with cerebral palsy and multidrug-resistant bacterial pneumonia treated with bacteriophage therapy: a case report.
    Lu Wang, Chunyan Lu, Huiwen Li, Dan Li.
       Background: Children with cerebral palsy (CP) are at high risk of pulmonary infection with multidrug-resistant organisms (MDROs) owing to recurrent infections, prolonged hospitalization, and repeated antibiotic exposure. Bacteriophage (phage) therapy has emerged as a promising alternative for infections refractory to conventional antibiotics; however, its application in children with CP complicated by multidrug-resistant pneumonia has rarely been reported, and corresponding nursing experience remains scarce.
    Case presentation: This report describes the nursing care of a 2-year-and-4-month-old boy with CP, secondary epilepsy, and severe pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and Staphylococcus aureus (discharge diagnosis: methicillin-resistant S. aureus infection), in whom conventional antibiotic therapy had failed. After comprehensive eligibility assessment, percutaneous endoscopic gastrostomy (PEG)-based nutritional optimization, and written informed consent, the child received a pre-planned 3-day course of nebulized phage cocktail therapy. Nursing care integrated standardized phage aerosol administration, staged enteral nutritional support, and family-centered health education. After treatment, A. baumannii was eradicated from bronchoalveolar lavage fluid, and subsequent A. baumannii isolates were susceptible to imipenem and meropenem (MIC ≤ 0.25 μg/mL, versus ≥16 μg/mL before therapy); CRKP was not re-isolated, and later S. aureus isolates were oxacillin-susceptible. Body temperature normalized, peripheral oxygen saturation remained stable without supplemental oxygen, and inflammatory markers decreased markedly. Body weight increased from 13.40 kg to 14.35 kg, and the nutritional risk score (STAMP) decreased from 5 (high risk) to 3. The child was discharged after 58 days of hospitalization.
    Conclusion: This case suggests that a structured nursing pathway embedding nebulized phage therapy is feasible and effective in medically complex children and may inform the care of similar pediatric cases.
    Keywords:  aerosol inhalation; bacteriophage therapy; case report; cerebral palsy; enteral nutrition; multidrug-resistant organisms; nursing
    DOI:  https://doi.org/10.3389/fped.2026.1955901
  9. Microbiol Spectr. 2026 Oct 22. e0206826
    Isolation and genomic characterization of a novel Pseudomonas jumbo phage ΦBRkr.
    Yoshiaki Sakata, Tomohiro Nakamura, Jumpei Fujiki, Kohana Tamamura, Natsuko Ichikawa, Keisuke Nakamura, Tomohito Iwasaki, Hidetomo Iwano.
      Jumbo phages generally have large viral genomes packaged in large virions and exhibit a broad host spectrum. However, the detailed variation in host spectrum among jumbo phages, particularly in the context of bacterial phage defense systems, is not fully understood yet. In the present study, we isolated a novel Pseudomonas virus, ΦBRkr, from sewage water in Japan. Transmission electron microscopic analysis and whole-genome sequencing revealed that ΦBRkr is a jumbo phage with a total DNA length of 306,291 bp, and suggested a novel Pawinskivirus-like phage. Furthermore, ΦBRkr showed broader infectivity against 100 genetically diverse Pseudomonas aeruginosa clinical isolates (62.0% of host spectrum) compared with Phikzvirus ΦNK1 (40.0% of host spectrum). By examining the correlation between phage infectivity and the presence of predicted phage defense systems across these 100 strains in an exploratory screening, we found that among the 50 predicted defense systems evaluated, the Jumbo phage killer (Juk) AB system emerged as the potential candidate showing a distinct differential restriction between the two phages. While ΦNK1 completely failed to infect any strains harboring the predicted JukAB, ΦBRkr may evade this defense mechanism in some strains. Genomic comparisons revealed that, unlike ΦKZ and ΦNK1, ΦBRkr lacks a homolog of the KZ241 gene, which is known to trigger the JukAB system. It has been suggested that this absence likely confers a stealth advantage to ΦBRkr during P. aeruginosa infection. These results contribute to a deeper understanding of the diversity of Pseudomonas jumbo phages and provide insights into their advantageous properties for future applications.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen causing severe multidrug-resistant infections, making phage therapy a promising alternative treatment. Jumbo phages are attractive candidates because they typically infect a wide range of bacterial strains. However, bacteria constantly deploy diverse defense systems to block viral infections, which can limit therapeutic efficacy. In this study, we isolated a novel jumbo phage, ΦBRkr, which exhibits a broad intra-species host range, infecting 62.0% of 100 diverse clinical P. aeruginosa isolates tested. Our results suggest that its ability to effectively evade the predicted Jumbo phage killer (Juk) defense system, a robust barrier restricting other well-known jumbo phages, contributed to its broader host range. Viral genomic evidence implies this phage employs a natural stealth strategy by lacking the specific protein targeted by the putative Juk system. Uncovering how certain phages naturally bypass robust bacterial immunities provides critical insights for selecting and developing highly effective phages for future applications.
    Keywords:  JukAB; Jumbo phage killer (Juk); Miltoncavirus; Pawinskivirus; Pseudomonas aeruginosa; bacteriophage; phage resistance; phage therapy
    DOI:  https://doi.org/10.1128/spectrum.02068-26
  10. Microbiologyopen. 2026 Oct;15(5): e70443
    Mechanisms and Application of Bacteriophages in Regulating Intestinal Health of Livestock and Poultry.
    Manman Song, Yuying Fan, Liguo Zhang, Wenhao Qi, Lin Li, Gang Zhao, Jianwei He.
      The escalating crisis of antibiotic resistance has driven the global livestock and poultry industry to seek effective alternatives. Bacteriophages (phages) are promising candidates because their high host specificity allows targeted elimination of key intestinal pathogens, including Salmonella, Campylobacter, pathogenic Escherichia coli, and Clostridium perfringens, while sparing commensal microbiota. This review summarizes the mechanisms by which phages promote intestinal health in livestock and poultry, covering pathogen lysis, modulation of gut microbiota, reinforcement of the intestinal mucosal barrier, and regulation of host immune responses. Evidence from broiler chickens, weaned piglets, and ruminants shows that phage therapy can improve growth performance and help control diseases such as necrotic enteritis and edema disease. We further discuss how administration route, dosage, timing, and formulation affect intestinal delivery, and how encapsulation systems such as microcapsules and liposomes improve phage survival under gastrointestinal conditions. Strategies to delay resistance evolution through phage cocktails, and combinations of phages with probiotics or plant extracts, are also evaluated, with a staged screening framework proposed for assessing compatibility prior to field deployment. Because positive results dominate the controlled-trial literature, we critically appraise failed, limited, and non-durable in vivo trials, attributing these outcomes to rapid clearance, anti-phage immunity, inappropriate dosing, and spatial exclusion coupled with ecological mismatch. Commercial translation additionally depends on scalable production and downstream removal of endotoxins and host cell proteins at acceptable cost. Overcoming these challenges would allow phage-based interventions to serve as precision antibiotic alternatives that support sustainable animal farming and global food security.
    Keywords:  antibiotic alternatives; gut microbiota; intestinal pathogens; phage cocktail; phage therapy
    DOI:  https://doi.org/10.1002/mbo3.70443
  11. Cureus. 2026 Sep;18(9): e116330
    The Bidirectional Relationship Between Rheumatoid Arthritis and Periodontitis: Current Evidence and Clinical Implications.
    Naif A Alwithanani.
      Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that share several pathogenic, immunological, and environmental characteristics. Increasing evidence suggests that these conditions are linked through a potentially bidirectional relationship in which chronic periodontal inflammation may contribute to the initiation and progression of RA, whereas RA may predispose individuals to periodontal tissue destruction through systemic inflammation, immune dysregulation, and impaired oral hygiene. This narrative review summarizes the current understanding of the epidemiological association between RA and periodontitis and discusses the shared inflammatory pathways, including cytokine dysregulation, osteoclast activation, and altered host immune responses, that underlie both diseases. Particular emphasis is placed on the reciprocal influence of periodontitis on RA activity and the impact of RA on periodontal disease. Available evidence indicates that periodontal infection may amplify the systemic inflammatory burden and autoimmune responses, whereas chronic inflammatory changes associated with RA can accelerate periodontal tissue breakdown and increase the risk of disease progression. Emerging clinical evidence also suggests that periodontal therapy may serve as a valuable adjunct to conventional RA management by reducing the systemic inflammatory burden and improving disease activity, although definitive causal relationships have not yet been established. Periodontal therapy may have beneficial effects on systemic inflammatory markers and selected measures of RA activity, although the clinical significance and consistency of these effects remain uncertain. Recognition of this bidirectional association highlights the importance of interdisciplinary collaboration between dental professionals and rheumatologists to facilitate early diagnosis, comprehensive patient assessment, and development of integrated treatment strategies. Future longitudinal and interventional studies are warranted to clarify the causal mechanisms linking these conditions and determine whether improved periodontal health can contribute to better long-term outcomes in patients with RA.
    Keywords:  bidirectional relationship; inflammation; oral-systemic health; periodontal therapy; periodontitis; rheumatoid arthritis
    DOI:  https://doi.org/10.7759/cureus.116330
  12. J Biomed Mater Res B Appl Biomater. 2026 Oct;114(10): e70166
    Beyond Antibacterial Activity: Engineering Multifunctional Biomaterials for Multidrug-Resistant Infections.
    Ilker S Bayer.
      Antimicrobial resistance is increasingly limiting the effectiveness of conventional antibiotic therapy, particularly in chronic wounds, biofilm-associated infections, and implant-related infections. Antimicrobial biomaterials have emerged as promising alternatives; however, much of the field remains organized around material classes or pathogen killing alone, with comparatively limited consideration of the complex biological environment in which infection develops and persists. This review proposes a function-based framework in which antimicrobial biomaterials are designed as integrated therapeutic systems rather than as passive antimicrobial carriers. Six complementary engineering functions are identified: infection targeting, overcoming bacterial defenses, multimodal pathogen eradication, host immune modulation, tissue regeneration, and adaptive or stimuli-responsive behavior. For each function, key design principles, representative strategies, and translational challenges are critically examined. Particular attention is given to the extent to which these functions have been experimentally integrated, including a systematic assessment of demonstrated versus largely conceptual pairwise combinations. Because the relative importance of each function varies by clinical application, the review also considers how these priorities shift across tissue and device context, including skin and soft tissue, bone, and short-term devices such as indwelling catheters. Rather than emphasizing efficacy alone, the review also examines translational limitations and failure points, including inadequate activity against clinically relevant organisms, limited clinical validation of established antimicrobial technologies, and regulatory failure of promising antimicrobial candidates. These examples highlight the persistent gap between laboratory performance and clinical utility. The review further considers the emerging tension between broad-spectrum antimicrobial strategies and approaches designed to preserve the host microbiome through species-selective targeting. Special emphasis is placed on halogen-based antimicrobial systems, catalytic nanozymes, and the emerging application of artificial intelligence to biomaterial design. Finally, a prioritized roadmap is proposed for advancing multifunctional antimicrobial biomaterials from mechanistic proof-of-concept toward clinically relevant therapeutic systems, while identifying key assumptions and knowledge gaps that remain to be validated.
    Keywords:  antimicrobial resistance; biofilm disruption; clinical translation; host immune modulation; multifunctional biomaterials; stimuli‐responsive systems; tissue regeneration
    DOI:  https://doi.org/10.1002/jbm.b.70166
  13. ACS Omega. 2026 Oct 13. 11(40): 60505-60521
    Bacterial Defense and Phage Counterdefense: Unraveling the Molecular Basis of Phage Resistance.
    Kunal Dutta, Kira M Velieva, Ekaterina V Skorb, Sergey Shityakov.
      Phage therapy represents a promising strategy against multidrug-resistant bacteria, but its clinical effectiveness is increasingly compromised by the emergence of phage-resistant traits (PRTs). This resistance develops through multiple interconnected mechanisms that operate at different levels of bacterial defense. At the primary level, mutations in phage receptors, cell surface glycoconjugates (lipopolysaccharide, capsule polysaccharide, exopolysaccharide), outer membrane proteins, drug efflux pumps, and surface layer proteins provide the first line of defense by preventing phage adsorption. These receptors are highly diverse across Gram-negative bacteria, Gram-positive bacteria, and acid-fast bacteria, with PRT being particularly dominant in Gram-negative species. At the secondary level, bacteria deploy sophisticated antiphage defense (APD) systems, including CRISPR-Cas, restriction-modification systems, and abortive infection mechanisms. The recent discovery of over 150 distinct APD systems underscores the remarkable complexity of bacterial immunity. Concurrently, bacteriophages have evolved anti-antiphage defense (AAPD) systems to counter bacterial immunity, establishing a dynamic coevolutionary arms race. This continuous interplay between APD diversification and AAPD counteradaptation drives the rapid emergence of PRT, which threatens the long-term viability of phage therapy. This systematic review examines the molecular basis of phage resistance across diverse bacterial taxa, analyzes the evolutionary and coevolutionary forces shaping APD and AAPD systems, and highlights previously overlooked aspects of phage-bacteria interactions. By integrating these perspectives, we aim to inform strategies for advancing modern phage therapy and guiding future research directions.
    DOI:  https://doi.org/10.1021/acsomega.6c00530
  14. Microb Pathog. 2026 Oct 19. pii: S0882-4010(26)00609-1. [Epub ahead of print]221 108883
    Salmonella phage characterization and host-dependent responses relevant to cocktail formulation.
    Yuechong Liu, Xi Liu, Song Zhang, Juhee Ahn.
      This study was characterized infection efficiency, replication kinetics, environmental tolerance, and host-associated responses of six Salmonella phages (Yrd1, Yrd2, NB1, NB2, NB3, and FPU) as candidate parameters relevant to cocktail formulation. All phages belong to the class Caudoviricetes, comprising five myovirus-like and one siphovirus-like (NB3) morphotype, with capsid dimensions of 38-74 nm in width and 46-94 nm in length, and tail lengths of 78-109 nm. Multiplicity of infection (MOI) assays (0.001-10) showed that low MOI conditions (0.001-0.01) produced higher phage amplification, whereas a high MOI (10) markedly reduced amplification, indicating reduced infection efficiency at higher phage-to-host ratios. One-step growth analysis (MOI 0.1) showed phage-specific latent periods ranging from 10 to 30 min. Burst size ranged from 15 to 389 PFU/cell, with Yrd2 and NB1 showing the two highest values. Stability assays showed phage-specific responses. FPU displayed the broadest pH tolerance profile in the plotted comparison, retaining normalized infectivity from pH 5 to 10, and showed the highest plotted normalized infectivity at 50-60OC. All six phages showed near-zero normalized infectivity at pH 2-3, pH 11-12, and 70OC. Network-based interaction analysis showed broader OD-based inhibitory connectivity for selected cocktails than for monophages across PU13036, EN, KE, and TY. On PU519, specific FPU-containing combinations showed reduced inhibition, but these effects are not interpreted as mechanistic phage-phage antagonism or generalized beyond the tested host. Because the assays used different host backgrounds, these measurements provide candidate parameters for future cocktail-selection studies, but their predictive value requires further validation.
    Keywords:  Bacteriophage therapy; Host range expansion; Network analysis; Phage cocktail design; Phage infection efficiency
    DOI:  https://doi.org/10.1016/j.micpath.2026.108883
  15. PeerJ. 2026 ;14 e21857
    Application of bacteriophages in the prevention of Bacillus cereus infection in potatoes.
    Xia Ji, Ting Zhang, Xiaoyu Hu, Danmei Li, Cuijie Zeng, Ruoqian Zeng, Weiwei Li, Tianshu Cai, Haiwei Xie.
       Background: The main component of potatoes is starch, which can serve as an easy breeding ground for Bacillus cereus during storage. This can decrease the shelf life of potatoes and pose food safety issues.
    Methods: This study isolated several strains of B. cereus from rotten potatoes in the market as well as one of their bacteriophages, Bacillus phage PHZU0001, from municipal sewage. The genome of Bacillus phage PHZU0001 was sequenced. The phage sensitivity to eight B. cereus strains was detected using plaque assay. Stability assays assessed the phage's thermal and pH tolerance.
    Results: The results showed that this bacteriophage had wide host range against B. cereus of different strains. Based on its genome sequence, this bacteriophage is from the Herelleviridae family. The biological characteristics of this bacteriophage indicated that it maintains stability at temperatures ranging from 23 °C to 50 °C and at pH levels ranging from 5 to 9. Inoculation of Bacillus phage PHZU0001 in potatoes effectively inhibited infection by B. cereus.
    Conclusion: This study identified a bacteriophage with a wide host range against B. cereus with potential applications in food storage and food safety.
    Keywords:  Bacillus cereus; Bacteriophages; Food safety; Herelleviridae; Potatoes
    DOI:  https://doi.org/10.7717/peerj.21857
  16. iScience. 2026 Nov 20. 29(11): 117433
    Microbiota-constrained bacterial density limits phage infection in the gut and allows persistence of susceptible cells.
    Anouk Bertola, Nicolas Wenner, Leonardo Lemos Rocha, Timothy G Keys, Médéric Diard.
      With the rise of antibiotic resistance, bacteriophage-based treatments against bacterial infections have regained momentum. However, phage therapy has so far shown only moderate success in complex environments like the mammalian gut, where phages are particularly promising tools for microbiome engineering and specific elimination of opportunistic pathogens. Here, we use different murine models of intestinal colonization to quantitatively assess the minimal population size of susceptible Escherichia coli cells that is required for phage replication in the gut (replication threshold). We found that the composition of the intestinal microbiota is a key factor shaping phage-bacteria interactions by restricting the carrying capacity of susceptible host cells. We further demonstrate that the replication threshold enables coexistence of susceptible and resistant bacteria in phage-treated mice, with implications for phage-based applications in complex environments like the gut.
    Keywords:  Escherichia coli; bacteriophage; gut colonization; in vivo evolution; microbiota; phage resistance
    DOI:  https://doi.org/10.1016/j.isci.2026.117433
  17. J Assoc Physicians India. 2026 Sep 01. 74(9): 15-18
    Integrated Genomic Phenotypic and Host-response Analysis of Multidrug-resistant Diabetic Foot Infections: A Tertiary Center Study from Kerala India.
    Mohammed Jaseem Ibrahim K.
       Background: Diabetic foot infections (DFIs) are a primary driver of amputation, worsened by multidrug-resistant (MDR) organisms. The link between pathogen genomics, virulence (e.g., biofilm), and host immunity is poorly quantified. This study aimed to integrate these multi-omic data streams to identify predictors of treatment failure.
    Materials and methods: This prospective, single-center cohort study enrolled 150 DFI patients. Deep-tissue and autologous healthy-skin biopsies were collected. Pathogens were identified (culture/16S rRNA), with susceptibility and biofilm capacity tested. MDR isolates (n = 76) underwent whole-genome sequencing (WGS). Host response was quantified using an eight-gene quantitative reverse transcription polymerase chain reaction (qRT-PCR) panel, normalized to autologous controls. The primary outcome was "healing failure" (amputation or persistent ulcer) at 12 weeks. A least absolute shrinkage and selection operator (LASSO)-penalized regression model was developed and cross-validated.
    Results: The final analytical cohort included 112 culture-positive patients; 68/112 (60.7%) had an MDR infection. WGS identified high-risk clones (Escherichia coli ST131, Klebsiella pneumoniae ST258). Healing failure occurred in 34/112 (30.4%) patients. Strong biofilm production (adjusted OR 3.81, 95% CI 1.92-7.55) and a high host IL-10:TNF-α expression ratio (AOR 2.98, 95% CI 1.41-6.30) were independent predictors of healing failure. The LASSO model achieved an optimism-corrected area under the curve (AUC) of 0.79 (95% CI 0.71-0.87) with acceptable calibration (Brier score: 0.18; slope: 0.95).
    Conclusion: In this DFI cohort, pathogen biofilm capacity and a modulated host immune signature were independently associated with treatment failure, highlighting potential new diagnostic and therapeutic targets.
    Keywords:  Biofilms; Diabetic foot infection; Host-pathogen interactions; Interleukin-10; Multidrug-resistant; Predictive model; Wound healing
    DOI:  https://doi.org/10.59556/japi.74.1693
  18. Microbiome Res Rep. 2026 ;5(3): 23
    The microbiome bone axis in osteomyelitis: integrating evidence from bone oral and gut microbiota.
    Chanon Kunasol, Chaloemwut Piyaphattachai, Jirawat Saengsin, Nipon Chattipakorn, Siriporn C Chattipakorn.
      Osteomyelitis is an inflammatory bone disorder that includes both infectious and noninfectious forms and remains a major cause of bone destruction, impaired skeletal repair, and long-term disability. Although bacterial infection is the predominant cause, disease progression is influenced by interactions among microorganisms, host immunity, inflammation, and bone remodeling. This review critically evaluates current evidence from genome-wide association and Mendelian randomization studies, clinical investigations, and experimental animal models. Clinical studies demonstrate that osteomyelitic bone contains polymicrobial communities enriched with anaerobic and biofilm-forming bacteria, whereas oral microbial dysbiosis differs between chronic bacterial and chronic nonbacterial osteomyelitis. Experimental studies indicate that gut microbial dysbiosis is associated with impaired intestinal barrier function, altered microbial metabolites, systemic inflammation, and delayed bone repair. Current evidence therefore suggests that microbial communities detected at local sites are associated with infection, biofilm formation, and local inflammatory responses, whereas the gut microbiome may influence systemic immunity, inflammatory tone, and bone remodeling. Although microbiome-targeted interventions have shown beneficial effects in experimental models, current evidence remains largely associative, and mechanistic and longitudinal studies are limited. A better understanding of microbiome-host interactions may facilitate the development of microbiome-based strategies for the prevention and treatment of osteomyelitis.
    Keywords:  Osteomyelitis; chronic bacterial osteomyelitis; chronic nonbacterial osteomyelitis; dysbiosis; microbiome-bone axis
    DOI:  https://doi.org/10.20517/mrr.2026.63
  19. J Vis Exp. 2026 Oct 16.
    High-Throughput Spot Assay for Isolation of Bacteriophages Against Multiple Host Strains from Environmental Samples.
    Xiaofu Wan, Yukun Zeng, Shuhong Han, Zixun Lin, Xiangke Duan, Min Ming, Wenheng Gan, Hongzhou Lu, Jiayin Shen.
      Phage therapy has emerged as a promising option for treating infections caused by multidrug-resistant bacteria, offering an alternative to conventional antibiotics. However, conventional isolation methods are laborious and tend to favor dominant host-phage pairs, limiting the diversity of recoverable phages. Expanding the collection of phages is therefore a critical step toward advancing phage-based therapies. To achieve effective isolation outcomes, it is essential to systematically screen environmental samples against a broad range of host strains under standardized conditions. The efficiency of phage recovery depends on several factors, including enrichment strategies, host range coverage, and infection dynamics. To address these challenges, we have developed a streamlined protocol that integrates liquid culture enrichment, polyethylene glycol (PEG)-mediated concentration, high-throughput spot screening on multiple host bacterial lawns, and subsequent streak purification for clonal isolation. This approach enables simultaneous screening of environmental samples against multiple pathogens in a single experimental setup, improving isolation efficiency. Notably, it enhances the recovery of phages with diverse host ranges. Our integrated workflow can reduce manual effort and material consumption and shorten the isolation period compared with conventional methods. This robust and evidence-based method accelerates the discovery of phages with potential applications in therapy and biocontrol. We anticipate that this protocol will prove particularly useful for building phage biobanks, preparing personalized phage therapeutics, and conducting large-scale environmental phage mining. Ultimately, it will help expand the repertoire of characterized phages for combating antimicrobial-resistant bacterial infections.
    DOI:  https://doi.org/10.3791/73287
  20. Front Microbiol. 2026 ;17 1906281
    Formulation, physicochemical characterization, and antimicrobial evaluation of drug-loaded essential oil microemulsions against Methicillin-resistant Staphylococcus aureus -associated diabetic foot ulcer infections.
    Disha Pramanick, Natarajan Chandrasekaran.
      Diabetes Mellitus, a leading endocrine disorder characterized by persistent hyperglycemia, ischemia, and neuropathy, causes ulcerative wounds that are often colonized by multidrug-resistant pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA), which exacerbate wound infections and can lead to complications such as sepsis and necrosis in Diabetic Foot Ulcers (DFU). This study aims to formulate phytochemical-based nanovesicle carriers for potential wound-healing applications to retain the therapeutic effects of antimicrobial compounds with their localized delivery. This investigation develops microemulsions containing Eugenol, Clove, and Cinnamon oils to encapsulate Vancomycin and Methicillin, preserving their antibacterial activity while providing sustained delivery to the site of action. Microemulsions tested for thermodynamic stability, DLS, zeta potential, pH, FTIR, and TEM, showed optimal hydrodynamic size and PDI (within 30 nm and 0.5), a more negative zeta potential of around -19 mV, and an acidic pH. FTIR of blank emulsions against drug modifications confirmed successful drug incorporation, and TEM showed spherical-oval morphology. Antimicrobial testing using AST, MIC, Antibiofilm, Checkerboard, and Time-kill assays showed that drug-loaded emulsions provided measurable in vitro antibacterial activity against the tested clinical MRSA isolates, with activity varying by formulation and isolate (Eug-Van in MRSA-CI 1 and Clo-Van in MRSA-CI 2). Meanwhile, for Methicillin formulations, Clo-Met showed measurable inhibition against both tested isolates. Release kinetics revealed that drug-loaded emulsions showed sustained, diffusion-controlled release of the active therapeutics - Vancomycin and Methicillin over 24 h, with slowly increasing concentrations initially, followed by a plateau with maximum release in the case of Eug-Van microemulsion. These results demonstrate the considerable potential of these drug-loaded microemulsions as advanced nanocarrier systems for localized antimicrobial delivery in MRSA-colonized DFU infections.
    Keywords:  MRSA; antibacterial efficacy; antibiotics; cinnamon; clove; controlled release; eugenol; microemulsion
    DOI:  https://doi.org/10.3389/fmicb.2026.1906281
  21. J Oral Microbiol. 2026 ;18(1): 2745592
    Invasive guests: the role of non-oral bacteria in oral dysbiosis and systemic health.
    Marzie Mahdizade Ari, Ali Al-Ahmad, Fabian Cieplik, Konstantin Johannes Scholz.
       Background: The human oral cavity harbors a diverse microbiota essential for maintaining oral and systemic health. While most resident microorganisms are commensals adapted to specific oral niches, increasing evidence highlights the presence of non-oral bacteria, including Helicobacter pylori, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacteriaceae, Staphylococcus aureus, Acinetobacter baumannii, Enterococcus faecalis and Clostridioides difficile. Traditionally associated with other body sites, these bacteria may enter the oral cavity and, under favorable ecological conditions, persist through mechanisms such as biofilm formation, stress tolerance, entry into a viable but non-cultivable (VBNC) state, coaggregation with the oral microbiota, and evasion of host immune responses. Their colonization has been reported particularly in dysbiotic oral environments, including periodontitis and immunocompromised conditions, where overgrowth may also facilitate their recovery by conventional culture methods.
    Objective: This review aims to summarize the current evidence on the presence, persistence mechanisms, clinical significance, and detection challenges of non-oral bacteria in the oral cavity, and to highlight the need for integrated diagnostic approaches.
    Design: A comprehensive literature review was conducted focusing on studies reporting the isolation, detection, and clinical relevance of non-oral opportunistic bacteria in the oral cavity, with emphasis on culture-based and molecular diagnostic methods.
    Results: Clinically, non-oral bacteria presence has been associated with dental caries, periodontal disease, endodontic infections, systemic dissemination, and their potential role as reservoirs of antibiotic resistance genes. Although several non-oral opportunistic bacteria can be readily isolated by culture when present at sufficient abundance, particularly in immunocompromised patients, detection may remain challenging in healthy individuals or low-biomass samples because of their transient or low-abundance occurrence, increasing the risk of misinterpretation.
    Conclusions: Recognizing the oral cavity as a dynamic niche for non-oral bacteria underscores the need for integrated culture- and molecular-based diagnostic approaches, improved infection control strategies, and further research into their pathogenic potential.
    Keywords:  Non-oral bacteria; antibiotic resistance; biofilm formation; microbial colonization; opportunistic pathogens; oral dysbiosis; oral microbiome
    DOI:  https://doi.org/10.1080/20002297.2026.2745592
  22. J R Soc N Z. 2026 Oct;56(5): e70087
    Emerging Molecular Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens: A Comprehensive Review.
    Tejpal Sharma, Indresh Kumar Maurya, Pankaj Chandley.
      The rise of antimicrobial resistance has marked ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of broad-spectrum antibiotic-based treatment. Moreover, the misuse and overuse of antibiotics have further complicated the management of bacterial infections by enhancing the risk of secondary infections. Despite traditional antibiotic development, there is a need for novel strategies to tackle the rising menace of ESKAPE pathogens. During the past few decades, various cellular and molecular-level investigations based on multidrug-resistant bacterial species have emerged. These investigations have played a major role in unraveling the intrinsic pathways that are involved in conferring AMR to ESKAPE pathogens. The molecular mechanisms of AMR in ESKAPE involve expression of efflux pumps, persistent biofilms, enzymatic drug inactivation, alterations in antibiotic targets, genetic mutations, and horizontal gene transfer. This review highlights the major molecular mechanisms of antimicrobial resistance in ESKAPE pathogens. By understanding these mechanistic pathways, more specific/targeted diagnostics and therapeutic approaches may be developed. This review outlines key findings from recent research studies on AMR trends in ESKAPE pathogens. This comprehensive review also provides current research gaps and future directions for combating AMR.
    Keywords:  ESKAPE; antimicrobial resistance; bacteria; drugs; multidrug resistant; pathogens
    DOI:  https://doi.org/10.1002/snz2.70087
  23. Cent European J Urol. 2026 ;79(3): 463-471
    Impact of the urinary microbiome on urinary tract infection progression.
    Szymon Karol Domagała, Kamil Kania, Jakub Nocoń, Artur Spyrka, Mateusz Marcinek, Michał Tkocz.
       Introduction: Urinary tract infections (UTIs) remain a significant challenge in modern urology, increasingly complicated by the shift away from the "sterile bladder dogma." This narrative review summarizes current knowledge (2020-2026) on the urinary microbiome in women, men, and children, emphasizing the transition toward personalized urological care.
    Material and methods: We conducted a comprehensive synthesis of 48 peer-reviewed articles from PubMed, Scopus, and Google Scholar. This narrative review evaluates the interplay between the urinary microbiome, host immune response, and pathogen virulence, while critically comparing traditional urine cultures with advanced diagnostic tools, such as next-generation sequencing (NGS) and expanded quantitative urine cultures (EQUC).
    Results: Our analysis highlights the role of dysbiosis in UTI progression and the increasing threat of multidrug-resistant pathogens within the ESKAPEE group. Findings reveal that while modern diagnostics offer a more detailed microbial profile, clinical implementation remains constrained by technical and standardization challenges.
    Conclusions: Standard urine culture may be insufficient for managing recurrent or atypical UTIs. We advocate for a personalized diagnostic and therapeutic approach that integrates molecular insights, aiming to curb antibiotic overuse and improve patient outcomes in the era of rising drug resistance.
    Keywords:  antimicrobial resistance; expanded quantitative urine culture; microbial dysbiosis; next-generation sequencing; recurrent urinary tract infection
    DOI:  https://doi.org/10.5173/ceju.2026.0083
  24. Front Cell Infect Microbiol. 2026 ;16 1847743
    Molecular epidemiology of carbapenemase-producing gram-negative bacilli in diabetic foot infections: association with glycemic control.
    Gamal Othman, Abdelnaser A Badawy, Rasha Hamed Al-Serwi, Maysaa El Sayed Zaki, Noha Tharwat Abou El-Khier, Nashwa M Alkassaby, Mohamed Saleh Ismail.
       Background: Carbapenem-resistant Gram-negative bacilli are an increasing threat in diabetic foot ulcer (DFU) infections, limiting therapeutic options and worsening outcomes. However, data linking specific carbapenemase genes to clinical and metabolic factors remain limited.
    Objectives: To isolate Gram-negative bacilli from deep tissue biopsies of DFUs, determine carbapenem susceptibility by minimum inhibitory concentration (MIC) testing, detect major carbapenemase genes by multiplex qPCR, and evaluate their association with glycemic control and Wagner grade.
    Methods: This cross-sectional study included 150 patients with infected DFUs. Isolates recovered from tissue and other specimens were identified by standard microbiological methods, and carbapenem susceptibility was assessed by MIC testing. Multiplex qPCR was used to detect blaKPC, blaNDM, blaOXA-48, blaVIM, and blaIMP, and associations between resistance determinants and clinical variables were analyzed statistically.
    Results: The mean patient age was 56.4 ± 9.8 years, with a male predominance (61.3%), and high-grade ulcers (Wagner III-V) were present in 54.7% of patients. Klebsiella pneumoniae predominated (60.0%), followed by Pseudomonas aeruginosa and Escherichia coli (each 14.7%). Resistance to meropenem and imipenem was high (77.3% and 75.3%, respectively), and carbapenemase production was detected in 84.0% of isolates. blaKPC (28.0%) and blaNDM (24.0%) were the most prevalent genes and were significantly associated with phenotypic carbapenemase production (P = 0.002 and P = 0.006, respectively). Carbapenemase producers showed significantly higher fasting glucose and HbA1c levels than non-producers (P < 0.001), with no significant association observed for Wagner grade (P = 0.570).
    Conclusions: DFUs showed a high burden of carbapenemase-producing Gram-negative bacilli, driven mainly by blaKPC and blaNDM. Poor glycemic control was strongly associated with these resistant infections, underscoring the need for integrated metabolic management, molecular surveillance, and antimicrobial stewardship. These findings position glycemic control as a modifiable driver of antimicrobial resistance in DFUs.
    Keywords:  BlaNDM; HbA1c; Klebsiella pneumoniae; antimicrobial stewardship; blaKPC; carbapenem resistance; diabetic foot ulcer; gram-negative bacilli
    DOI:  https://doi.org/10.3389/fcimb.2026.1847743
  25. Can J Nurs Res. 2026 Oct 21. 8445621261498966
    Continuity of Chronic Wound Care Across Hospital-to-Home Transitions: A Qualitative Study of Hospital and Community Nurses' Experiences.
    Élodie Montaigne, Anne-Marie Ollitrault, Nsuni Met, Aline Corvol.
      AimTo explore how hospital nurses (HNs) and community nurses (CNs) in France manage chronic wound care for older adults across settings, and how their practices shape continuity of care during hospital-to-home transitions.DesignQualitative descriptive study combining ethnographic shadowing and a focus group.MethodsFieldwork took place in a French university hospital, across four units: acute geriatrics, rehabilitation, vascular surgery, dermatology. The focus group involved CNs from seven different self-employed nursing practices. We shadowed 15 HNs for approximately 92 h and conducted one focus group with 7 CNs. Data were analyzed inductively using constant comparison, with a second-stage interpretive analysis informed by Meleis' transitions theory.ResultsFour interconnected processes shaped continuity of chronic wound care across the transition: (1) nursing expertise in wound management was expressed differently across hospital and community settings; (2) discharge coordination was fragmented, with rare nurse-to-nurse communication and insufficient transfer of wound-specific information; (3) organizational logics diverged, with discontinuous hospital workflows and time-pressured, fee-for-service-constrained community visits; and (4) patient involvement during hospitalization was limited, constraining engagement and preparedness post-discharge. Continuity was frequently maintained through compensatory work from nurses.ConclusionContinuity of chronic wound care depends less on nursing expertise than on the organizational conditions enabling that expertise to be mobilized across settings.ImpactThis study highlights the need for more integrated transitional care, including clearer and more consistent responsibilities at discharge, structured nurse-to-nurse discharge communication, and earlier patient involvement in wound care management.
    Keywords:  Hospital-to-home transition; chronic wounds; community nurses; continuity of care; hospital nurses; older adults
    DOI:  https://doi.org/10.1177/08445621261498966
  26. Front Microbiol. 2026 ;17 1915213
    Biofilm-associated genes in Staphylococcus aureus: role in chronic infections and therapeutic challenges.
    Mohammad Asim Azhar, Tanveer Ahmad Mir, Sana Ahmed, Abdullah M Assiri, Dieter C Broering.
      One of the major contributors to persistent healthcare and community-associated infections is S. aureus, which has a remarkable ability to form biofilms that protect it against the host immune system and antimicrobial therapy. In recent years, it has become clear that biofilm development is a highly orchestrated and dynamic process, controlled by complex genetic networks, transcriptional regulators, two-component systems (TCSs), and environmental signals. The present review covers the molecular mechanisms involved in the initiation, maturation, maintenance, and dispersal of biofilms in general, and in particular, the coordinated functions of adhesins, the icaADBC operon, components of the extracellular matrix (ECM), global regulators (agr, sarA, and sigB), and two-component regulatory systems, as well as emerging insights from transcriptomic studies on biofilm adaptation. We then review the roles of these regulatory pathways in metabolic heterogeneity, antibiotic tolerance, immune evasion, and persistence in clinically relevant biofilm-associated infections, including infective endocarditis, osteomyelitis, prosthetic joint infection, catheter-associated infection, and diabetic foot infection. The review further outlines the latest developments in antibiofilm therapeutics, including matrix-degrading enzymes, quorum-sensing inhibitors, antimicrobial peptides, bacteriophage-based therapeutics, lysins, nitric oxide donors, nanoparticle-assisted therapeutics, and CRISPR-Cas-based antimicrobials. Incorporating molecular regulation into infection-specific pathogenesis and emerging therapeutic strategies, this review offers a new perspective on the biology of S. aureus biofilms and highlights opportunities to develop mechanism-based interventions to combat chronic biofilm-associated infections.
    Keywords:  Staphylococcus aureus; antibiofilm therapies; antibiotic tolerance; biofilm-associated genes; chronic infections
    DOI:  https://doi.org/10.3389/fmicb.2026.1915213
  27. Front Cell Infect Microbiol. 2026 ;16 1946319
    Periodontal diseases and coronary artery disease: epidemiological links, pathogenic mechanisms and prospects for comorbidity integrated management.
    Chengkui Xu, Tong Yu, Lulu Zhang.
      Periodontal disease (PD) and coronary artery disease (CAD) are two highly prevalent chronic systemic disorders with overlapping population risk profiles. Accumulating observational, cellular, and genetic studies have suggested potential positive correlations between PD severity, periodontal pathogen load, and CAD incidence, coronary lesion severity, and major adverse cardiac events, whereas Mendelian randomization analyses may not support a direct causal link between the two illnesses. Several synergistic pathogenic pathways may mediate their association: periodontal pathogens may translocate into peripheral circulation to colonize atherosclerotic plaques and exert potential direct vascular toxicity; sustained systemic low-grade inflammation may disrupt endothelial homeostasis; molecular mimicry may induce cross-autoimmune vascular impairment; shared susceptibility loci and conventional cardiovascular risk factors may jointly amplify vascular damage. Standard non-surgical periodontal therapy may reduce systemic inflammatory burden and improve endothelial function, and clinical and microbial periodontal markers may serve as non-invasive biomarkers for CAD risk stratification. This review synthesizes epidemiological evidence and multilayered pathogenic mechanisms and proposes bidirectional collaborative interventions and multidisciplinary cardiostomatological management frameworks for comorbid patients. Further large-scale randomized controlled trials and multi-ethnic genetic analyses are still required to clarify causal inference and potential long-term cardiovascular benefits of periodontal intervention.
    Keywords:  atherosclerosis; cardio-oral comorbidity; coronary artery disease; multidisciplinary management; periodontal disease; periodontal pathogens; systemic inflammation
    DOI:  https://doi.org/10.3389/fcimb.2026.1946319
  28. ACS Synth Biol. 2026 Oct 16. 15(10): 4307-4315
    Cell-free Engineering of LPST153 Bacteriophage Receptor-Binding Proteins Enables Tunable Host-Range Modulation.
    Bosma Jaap S, Noireaux Vincent, Bowden Steven D.
      Bacteriophages are increasingly explored and applied to combat antibiotic-resistant bacteria, yet rapid resistance development and narrow host range can limit their broader application. Engineering phage receptor-binding proteins (RBPs) to expand phage host ranges offers a promising strategy to overcome some of these constraints. However, current approaches remain labor-intensive and difficult to control. Here, we use a cell-free phage engineering workflow to rapidly modify and characterize the RBP of the Salmonella phage LPST153. Using the PHEIGES platform and engineering targeted RBP mutations, we identified residues 389 and 402 within the tail fiber as determinants of host specificity. The G389R substitution significantly increased phage adsorption (%), reaching 65% on E. coli BW25113 and 51% on the LPS-truncated E. coli BW25113 ΔwaaC, compared with 27% and 5.7% for the wild-type LPST153, respectively. Targeted engineering of tail fiber residue 389 generated phage variants with distinct host-range phenotypes, with a G389T variant that exhibited an alternative infection profile relative to G389R. Together, these findings demonstrate that minimal, site-specific modifications of RBPs can substantially modulate LPST153 host specificity. This work establishes a framework for rapid engineering of phages with tailored host ranges, advancing phage-based antimicrobial strategies.
    Keywords:  Salmonella; bacteriophage; cell-free expression; engineering; tail fiber
    DOI:  https://doi.org/10.1021/acssynbio.6c00515
  29. Sci Adv. 2026 Oct 23. 12(43): eaef9265
    Stable coexistence and transport of lytic phage infections with migrating bacterial hosts.
    Jacopo Marchi, Chadiga Khalek, Abir George, Joshua S Weitz, Remy Chait.
      Bacteriophages (phages), viruses that exclusively infect bacteria, coexist with their bacterial hosts across diverse environments at densities exceeding 107 per milliliter in marine surface waters, 108 per milliliter in soils, and 109 per milliliter in the human gut. In contrast, phage lysis of bacterial populations within well-mixed in vitro environments select for the emergence of phage-resistant bacterial mutants, which, in turn, select for host-range expansion phage mutants and, typically, the collapse of phage populations altogether. This gap in outcome raises a question: What enables long-term phage-bacteria coexistence? Here, we show how interactions in space can facilitate stable coexistence and long-range transport of virulent phage along with migrating bacteria. Combining theory, simulation, and experiments across multiple phage-bacteria systems, we reveal a chemotaxis-driven mechanism that robustly stabilizes coexistence and dispersal of virulent phages with migrating hosts. These findings suggest the ecological relevance of spatial interaction mechanisms that reinforce stability between antagonistic partners in the absence of perpetual cycles of defense and counterdefense, which may be broadly applicable across phage-bacteria systems.
    DOI:  https://doi.org/10.1126/sciadv.aef9265
  30. Future Healthc J. 2026 Sep;13(3): 100560
    The forgotten organ: Why the oral microbiome belongs in every physician's toolkit.
    Victoria Sampson.
      The oral cavity is the most densely colonised microbial niche in the human body after the gut - over 700 species and an estimated two billion bacteria (Deo and Deshmukh, 2019) - yet it remains conspicuously absent from the systemic health conversation. Mounting evidence links oral microbial dysbiosis to more than 50 systemic conditions (Peng et al, 2022), including cardiovascular disease, type 2 diabetes (Preshaw et al, 2026), adverse pregnancy outcomes, rheumatoid arthritis and Alzheimer's. Despite this, dentistry and medicine continue to operate as parallel systems, with oral health excluded from most general health screens, NHS commissioning structures and undergraduate medical curricula. This narrative review analyses current evidence on the oral microbiome and oral-systemic disease, outlines three biological mechanisms by which the oral cavity drives systemic disease, and sets out five practical, author-proposed steps physicians can take to integrate oral health into routine practice. The case for action is no longer scientific - it is structural.
    Keywords:  Dysbiosis; Oral microbiome; Oral-gut axis; Oral-systemic health; Periodontitis; Preventive medicine
    DOI:  https://doi.org/10.1016/j.fhj.2026.100560
  31. J Am Assoc Nurse Pract. 2026 Oct 20.
    The use of technology to improve wound care practice.
    Anne Walsh.
       BACKGROUND: As clinicians we may encounter patients with complicated wounds of varying etiologies.
    LOCAL PROBLEM: Wound education is often lacking in nursing and medical curriculums. There is shortage of wound specialized clinicians to offer guidance. Furthermore, there is a shortage of palliative specialized clinicians to assist when the goals of wound care may need to shift to symptom management.
    METHODS: The accredited Wound Care Pro app was developed as an educational resource for clinicians to meet this critical care need. It includes an overview of eight wound etiologies with descriptions, images, treatment options, case studies, and interventions to manage distressing symptoms, such as wound pain, odor, bleeding, and excessive exudate.
    INTERVENTIONS: Technology was used to develop an educational tool for clinicians to have at their fingertips to help bridge the knowledge gap. The goals include empowering clinicians caring for patients with wounds to improve the healing potential when healing is the goal, to decrease the risk of complications, to improve symptom management, to decrease the wasteful use of costly wound supplies, and to decrease the risk of litigation from inappropriate wound care plans.
    RESULTS: More than 11,000 clinicians have downloaded the application with positive feedback received, including how it has helped them get more appropriate, cost-effective wound care plans in place.
    CONCLUSION: Although there is a shortage of wound and palliative specialized clinicians to meet complex patient wound care needs, technology can help empower clinicians whether wound healing or palliation is the goal.
    Keywords:  Palliative wound care; wound CME/CE credits; wound care app; wound care education; wound care technology
    DOI:  https://doi.org/10.1097/JXX.0000000000001383
  32. Environ Microbiol Rep. 2026 Oct;pii: e70445. [Epub ahead of print]18(5):
    Microbiome Continuum: Connecting Environmental, Host-Associated and Engineered Microbiomes Through One Health and Artificial Intelligence.
    Mohammad Nazrul Islam Bhuiyan.
      Microbiomes are increasingly understood as interconnected ecological systems spanning soil, water, plants, animals, humans and engineered environments rather than as isolated host-associated communities. This microbiome continuum provides a mechanistic perspective for One Health by linking microbial cells with the movement of metabolites, genes, signalling molecules and ecological functions across environmental boundaries. Here, we critically examined the biological processes that maintain this continuity, including dispersal, horizontal gene transfer (HGT), metabolic exchange, environmental exposure and host-microbe communication. We consider how climate change and anthropogenic disturbance reshape these interactions and influence antimicrobial resistance (AMR), non-communicable disease, ecosystem function and pathogen emergence. We further evaluate how artificial intelligence (AI), including machine learning and deep learning, can integrate multi-omics and longitudinal data, while emphasizing that predictive performance does not establish causality and that AI remains dependent on data quality, biological knowledge and experimental validation. Engineered microbiomes offer opportunities for targeted intervention, but ecological stability, biosafety, HGT and translational uncertainty remain important constraints. We propose a One Health Microbiome Intelligence Framework (OH-MIF) as a conceptual architecture for cross-domain integration, with emphasis on standardized data, causal validation, equitable participation and human oversight.
    Keywords:  artificial intelligence; environmental microbiology; microbiome continuum; multi‐omics; one health
    DOI:  https://doi.org/10.1111/1758-2229.70445
  33. J Natl Med Assoc. 2026 Oct 22. pii: S0027-9684(26)00176-8. [Epub ahead of print]118(6): 101107
    Diverging mortality pathways for chronic wounds: A 26-year analysis of United States national data, 1999-2024.
    F N U Vinika, V Kumar, R Kumar, F N U Tisha, M Yaseen, P Wadhwani, F Qureshi, S Rukh, D Kumar Alias Sailish, T Ali, H Kumar, V Anand, A Tesfaye.
       BACKGROUND: Pressure ulcers (PUs) and chronic non-healing wounds (NHWs) are common, costly, and often fatal conditions among older adults living with multiple illnesses. Although the two arise through distinct biological pathways, they are frequently reported together in a way that can obscure how each is actually trending. We separated the two conditions and examined their mortality trajectories across 26 years of United States national data.
    METHODS: Using the CDC WONDER database, we retrospectively analyzed death records from 1999 through 2024. Pressure ulcers were identified by ICD-10 code L89; non-healing wounds by codes L97 or L98.4. Each condition was treated as an independent primary outcome rather than being merged into a single indicator. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 population were computed against the 2000 U.S. standard population, and Joinpoint regression applying a grid search across zero to three joinpoints with permutation-based model selection was used to characterize temporal trends. Subgroup rates by demographic and geographic strata are reported for the combined wound-associated decedent population as a whole, since suppression of small cell counts precludes stable code-specific estimation within narrower strata.
    RESULTS: Pressure ulcers appeared on 255,054 death certificates (AAMR 2.8 per 100,000; 95% CI 2.7-2.9), while non-healing wounds appeared on 69,230 (AAMR 0.7; 95% CI 0.7-0.7); only 5834 decedents (1.8%) carried codes for both. Annual PU deaths increased 1.3-fold, from 9154 in 1999 to 12,016 in 2024, peaking at 13,411 in 2022; NHW deaths rose 2.6-fold over the same span, from 1792 to 4703. As a proportion of all wound-associated deaths, the NHW share climbed from 16.5% to 28.6%. NHW mortality has climbed steadily since 2012, with the AAMR moving from 0.6 to 1.1 per 100,000 (APC 5.64; p < 0.000001). For the combined wound-associated cohort, the AAMR declined from 4.0 in 1999 to 3.1 in 2018 (APC -1.22; 95% CI -1.94 to -0.31; p = 0.042), climbed to 4.2 by 2022, and eased slightly to 3.9 by 2024, though neither of the latter two shifts reached statistical significance (p = 0.151 and p = 0.237, respectively). Mortality rose sharply with age, reaching a crude rate of 82.5 per 100,000 among those 85 and older. AAMRs were comparable between men (3.4; 95% CI 3.4-3.5) and women (3.5; 95% CI 3.4-3.6); early-period declines reached significance in women (APC -1.20, p = 0.024) but not men (APC -1.02, p = 0.051). The highest rates were observed among Black or African American (9.8; 95% CI 9.4-10.2) and American Indian or Alaska Native (5.6; 95% CI 4.4-6.8) populations, while the Asian or Pacific Islander rate was lowest and declined significantly across the full period (1.6; 95% CI 1.3-1.8; APC -0.94, p = 0.022). Rates were highest in the South (4.2; 95% CI 4.1-4.3), which rose significantly after 2016 (APC 4.25, p = 0.0008), and in non-metropolitan counties (3.7; 95% CI 3.5-3.8), which overtook metropolitan rates (3.5; 95% CI 3.4-3.5) after 2008.
    CONCLUSIONS: Pressure ulcer and non-healing wound mortality followed opposite 26-year trajectories, arguing against a single pooled measure. The rising non-healing wound share and persistent racial, regional, and urban-rural disparities support condition-specific prevention and broader access to wound care. These descriptive findings should be interpreted as associations, not causal effects.
    Keywords:  Chronic non-healing wounds; Mortality trends; Pressure ulcers; United states
    DOI:  https://doi.org/10.1016/j.jnma.2026.101107
  34. Spine J. 2026 Oct 18. pii: S1529-9430(26)00709-6. [Epub ahead of print]
    Management Strategies and Clinical Outcomes of Methicillin Resistant Staphylococcus Aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-Analysis.
    Farzad Pourghazi, Seyed Mohammad Amin Alavi, Georges Baaklini, Ahmad Nassr, Brett A Freedman, Takahiro Matsuo, Aaron J Tande, Elie F Berbari.
       BACKGROUND CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of native vertebral osteomyelitis (NVO) and is associated with persistent infection, complications, prolonged hospitalization, and increased mortality.
    PURPOSE: We conducted this systematic review and meta-analysis to evaluate the antimicrobial and surgical approaches used for MRSA NVO and their associated clinical outcomes.
    STUDY SETTING: Systematic review and meta-analysis.
    METHODS: A systematic literature search of MEDLINE, Scopus, and Web of Science was conducted on November 27, 2025. Studies were eligible if they included adults with MRSA NVO, evaluated medical or surgical treatment strategies, reported clinical outcomes, and included at least five patients. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using the Newcastle-Ottawa Scale and the Murad et al. tool. Random-effects models were used to pool proportions of treatment success, reinfection, and mortality.
    RESULTS: Thirty studies including 677 patients were included. Treatment strategies were heterogeneous and included prolonged anti-MRSA antimicrobial therapy and surgical approaches ranging from debridement and drainage to decompression and spinal stabilization or fusion. Vancomycin-based regimens were the most frequently reported antimicrobial strategy. Among studies reporting treatment duration, intravenous therapy commonly ranged from 4 to 8 weeks, with some patients receiving oral step-down or suppressive therapy. The pooled treatment success rate was 84.9% (95% CI, 76.7%-90.7%), pooled reinfection rate was 15.3% (95% CI, 9.5%-23.6%), and pooled mortality rate was 3.1% (95% CI, 0.8%-10.8%). Subgroup analyses were not feasible because treatment-specific data were limited and inconsistently reported.
    CONCLUSIONS: Management of MRSA NVO varied substantially across studies, with vancomycin-based antimicrobial therapy and diverse surgical strategies commonly reported. Pooled outcomes showed high treatment success with lower rates of reinfection and mortality. The substantial clinical and methodological heterogeneity of the available evidence highlights the need for prospective studies with standardized treatment and outcome reporting.
    Keywords:  Meta-analysis; Methicillin resistant; Native vertebral osteomyelitis; Outcome
    DOI:  https://doi.org/10.1016/j.spinee.2026.10.007
  35. Appl Microbiol Biotechnol. 2026 Jul 28. pii: 318. [Epub ahead of print]110(1):
    Comparative purification of a Salmonella bacteriophage for protein profiling.
    Alinur Toleukhan, Akbope Abdykalyk, Aktoty Anarbekova, Azamat Abdimukhtar, Bekzat Yerzhigit, Nazym Syrym, Nadezhda Zinina, Sabira Alpysbayeva, Makhpal Sarmykova, Yeldos Serikbay, Kali Tileukhanov, Nurlan Kozhabergenov, Bekbolat Usserbayev, Yeraly Shayakhmetov, Kuandyk Zhugunissov, Sergazy Nurabayev, Andrey Shestakov, Bolat Yespembetov.
      Salmonella enterica bacteriophages are increasingly studied for bacterial biocontrol and applied microbiology. However, reliable downstream characterization depends strongly on how the phage material is purified and concentrated. This study compared five preparation strategies for a Salmonella bacteriophage: sucrose density gradient centrifugation, cesium chloride gradient centrifugation, ultrafiltration followed by lyophilization, ultrafiltration followed by ammonium sulfate precipitation, and ultrafiltration followed by trichloroacetic acid precipitation. The preparations were assessed for infectious phage recovery, total protein concentration, SDS-PAGE protein profiles, an exploratory molecular weight-based comparison with a reference phage dataset, and targeted real-time PCR screening for selected virulence-associated determinants. Ultrafiltration followed by ammonium sulfate precipitation gave the highest infectious phage recovery among the infectivity-preserving workflows and produced a consistent eight-band SDS-PAGE profile. Trichloroacetic acid precipitation produced a similar banding pattern but was considered mainly a protein precipitation method because of its denaturing effect. Cesium chloride gradient centrifugation gave the most complex SDS-PAGE profile, while ultrafiltration followed by lyophilization gave the least resolved one. Several bands fell within the molecular-mass ranges reported for proteins of related Salmonella phages, but matching by molecular mass alone cannot identify the proteins, which would require LC-MS/MS. Targeted real-time PCR did not detect sopE, sspH1, sseI, or sopE2. Under the conditions tested, ultrafiltration followed by ammonium sulfate precipitation gave the highest infectious recovery and a consistent SDS-PAGE pattern; these results describe how the workflows behaved here rather than showing that one method is generally superior. KEY POINTS: • Five workflows were compared for Salmonella phage purification. • Ammonium sulfate precipitation gave the highest infectious recovery. • Selected virulence-associated genes were not detected by qPCR.
    Keywords:   Salmonella bacteriophage; Bacteriophage purification; Molecular safety screening; Phage recovery; SDS-PAGE profiling; Ultrafiltration
    DOI:  https://doi.org/10.1007/s00253-026-13982-z
  36. Future Microbiol. 2026 Oct 20. 1-14
    Live biotherapeutics in the post-antibiotic era: exploring the potential of probiotics to counter multidrug resistance.
    Supriya Shidhaye, Anis Chaudhary, Yogendra Gautam, Vishal Chafle, Harshad Patil, Milind Umekar, Hassan Ahmed Rudayni, Rashmi Trivedi.
      Antimicrobial resistance (AMR) is a major global health threat that compromises the effectiveness of existing antibiotics and highlights the urgent need for alternative and adjunctive therapeutic strategies. Probiotics have emerged as potential adjunctive strategies because of their ability to modulate host-microbe interactions and influence microbial ecology without promoting resistance. This review examines the current evidence on the potential role of probiotics in combating multidrug-resistant organisms, based on findings from in vitro studies, animal models, and clinical investigations. The review is based on a narrative literature search of the PubMed database, covering studies published between 2020 and 2025, with earlier landmark studies. The mechanisms discussed include competitive exclusion of pathogens, the production of antimicrobial compounds, the enhancement of intestinal barrier function, and the modulation of host immune responses. In addition, probiotics are evaluated for their capacity to interfere with quorum sensing and inhibit biofilm formation, thereby reducing pathogen virulence and colonization. The review also addresses key limitations, including strain-specific variability, safety concerns in vulnerable populations, and the lack of standardized clinical protocols. Current evidence suggests that probiotics may represent a useful adjunct to existing AMR management strategies. However, their broader clinical application requires larger research to establish their efficacy and safety.
    Keywords:  Probiotics; antimicrobial resistance; gut microbiota; live biotherapeutic products; multidrug-resistant organisms
    DOI:  https://doi.org/10.1080/17460913.2026.2749225
  37. Transl Res. 2026 Oct 21. pii: S1931-5244(26)00216-1. [Epub ahead of print]
    From Hypoxia to Healing: Topical Deferoxamine Enhances Wound Closure and Neovascularization in Diabetic Animal Models - A Systematic Review and Meta-Analysis.
    Daniel Müller, Jens Klotsche, Lisa Blindzellner, Frank Buttgereit, Robert Sabat, Paula Hoff, Timo Gaber.
      Chronic wounds are a major health burden, affecting approximately 0.22% of the global population. Diabetic foot ulcers are particularly common and serious, due to their high risks of infection, amputation, and recurrence. Deferoxamine (DFO), an iron chelator that stabilizes hypoxia-inducible factor signaling and promotes angiogenesis, has been studied as a topical therapy to improve diabetic wound repair in preclinical studies. This systematic review and meta-analysis evaluates topical DFO in diabetic rat and mouse wound models. Following PRISMA guidelines and prospective PROSPERO registration, MEDLINE (PubMed), Embase, and Web of Science were systematically searched in November 2025. Internal validity was evaluated using the SYRCLE risk-of-bias tool. The primary endpoint was wound closure rate (%), and the secondary endpoint was neovascularization assessed by immunohistochemical quantification of CD31-positive vessels. Thirty-eight studies were included in the systematic review, and 29 provided sufficient data for meta-analysis. Topical DFO significantly improved wound closure (MD 13.26%, 95% CI 10.70-15.83) and increased neovascularization (SMD 2.39, 95% CI 1.64-3.14) compared to DFO-free controls (both p < 0.0001). Benefits were observed across diverse experimental settings and delivery systems. Subgroup findings further suggest that sustained local DFO availability may enhance efficacy. Topical DFO therapy demonstrates robust preclinical evidence for improving diabetic wound healing, supporting clinical translation. Future work should prioritize developing delivery platforms that enable controlled, prolonged local DFO exposure to maximize therapeutic benefit for patients with chronic wounds, especially those with diabetes.
    Keywords:  Deferoxamine; diabetes; neovascularization; preclinical models; regenerative medicine; wound healing
    DOI:  https://doi.org/10.1016/j.trsl.2026.10.006
  38. Hlife. 2026 Sep;4(9): 581-595
    A phage-based luminescent reporter platform for rapid typing of multiple capsular types of Klebsiella pneumoniae.
    Yiyao Song, Shisong Jing, Yi Li, Yinglu Guo, Jiangqing Huang, Xianbiao Bi, Dawei Wei, Chao Wang, Gang Zhang, Jiajia Zheng, Zhongrui Ma, Jie Feng.
      Klebsiella pneumoniae is an important opportunistic pathogen, and its capsular polysaccharides are key virulence factors. Capsular typing is important for epidemiological surveillance, clinical diagnosis, and therapy development; however, methods for capsule-targeted detection remain limited. Here, we engineered a modular bioluminescent reporter phage platform leveraging bacteriophage receptor-binding proteins (RBPs) for specific K. pneumoniae capsular typing. Initially, the K2-specific bacteriophage ΦRCIP0109 was engineered with the nluc reporter gene to generate ΦRCIP0109::nluc for K2 detection. Using ΦRCIP0109::nluc as the chassis, we engineered reporter phages by swapping RBPs, thereby expanding the detection range to four additional clinically important K-types (K64, K47, K1, and K57). Reporter phage specificity and sensitivity were evaluated against clinical isolates and in simulated polymicrobial environments. Directed evolution was employed to introduce RBP mutations for enhanced phage adsorption. These five reporter phages achieved 100% specificity against clinical isolates, detecting concentrations as low as 10 colony-forming units/mL within 3.5-5.5 h and successfully differentiating host strains in polymicrobial synthetic urine. Directed evolution of an RBP yielded a 10- to 100-fold increase in luminescence compared to that of the wild-type phage. Together, these advances establish a scalable platform that can be expanded to additional capsular types and the detection of other pathogens, representing a platform with clear potential for integration into point-of-care diagnostics, guiding targeted antimicrobial therapy and precision phage therapy.
    Keywords:  Klebsiella pneumoniae; capsular typing; directed evolution; receptor-binding proteins; reporter phage
    DOI:  https://doi.org/10.1016/j.hlife.2026.06.001
  39. J Vis Exp. 2026 Oct 21.
    Wound Position is Associated with Morphological Stability and Quantitative Accuracy in Murine Skin Healing Models.
    Ryoma Matsuzaki, Chen Chi, Rina Akashi, Keita Kobashi, Ryoichi Mori.
      Intractable skin ulcers, including diabetic foot and pressure ulcers, are impactful clinical challenges. Therefore, appropriate skin wound models are required to develop treatments that promote wound healing. Many studies have used mice with defects covering the entire skin thickness. However, the location of the wound varied depending on the study, such as the midline of the back of the mouse or wounds created bilaterally on both sides of the spine. Wounds at the midline of the back heal in a circular shape. However, wounds on both sides of the spine can be distorted by movement. Therefore, differences in the location of the wound affected closure. Furthermore, although closure rate is commonly used to evaluate wound healing, accurate quantification is difficult using conventional imaging because camera height is not consistent. The use of a digital camera designed for skin observation (Dermo camera) enables wound imaging from a fixed position. Therefore, this protocol proposes methods for selecting the optimal wound site and performing wound imaging that are suitable for evaluating wound healing in mice and for histological analysis of extracellular matrix remodeling, including re-epithelialization and fibrosis.
    DOI:  https://doi.org/10.3791/74246
  40. Pulmonology. 2026 Dec;32(1): 2742057
    Non-eligibility for highly effective modulator therapy with elexacaftor/tezacaftor/ivacaftor in cystic fibrosis: What about Portugal?
    Elsa Fragoso, Pilar Azevedo, Luísa Pereira, Telma Barbosa, Ana Lúcia Cardoso, Célia Maia Cruz, Adelina Amorim, Inês Azevedo, Leonor Almeida, Susana Castanhinha, Ana Sofia Santos, Fernanda Gamboa, Teresa Reis Silva, Cristina Freitas, Vitor Teixeira, Alexandra Carreiro, Juan Gonçalves.
       BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR modulators are drugs developed to target the defective protein. All over the world, there are patients considered non-eligible for this therapy according to local regulatory policies.
    METHODS: To characterise the Portuguese CF patients defined as non-eligible according to genotype for highly effective modulator therapy (HEMT) with elexacaftor/tezacaftor/ivacaftor (ETI), the authors conducted a multicentre observational study based on a retrospective analysis of the Portuguese CF population.
    RESULTS: Based on the current prescribing policy in Portugal, the prevalence of non-eligible patients in Portugal in 2023 was 18.7%, similar to that reported in Europe. However, the regulatory acceleration in the CFTR modulator landscape in 2025 will most likely decrease the expected prevalence to 1.2% under national regulatory adoption of EMA criteria. R334W, G85E, N1303K, G542X, A561E, R1066C and P205S are the most prevalent variants. Most patients are young adults with established pulmonary disease. CF therapies impose a considerable burden on this population.
    CONCLUSION: This study provides a deeper understanding of the Portuguese CF population currently ineligible for ETI and enables the projection of the potential impact that forthcoming changes in HEMT eligibility criteria may have across Portugal. With the anticipated expansion of these criteria, the number of patients remaining ineligible for HEMT is expected to become residual. Furthermore, the present work offers a characterisation of patients likely to remain ineligible for HEMT in the future, who could be suitable candidates for clinical trials exploring alternative therapeutic approaches.
    Keywords:  CFTR modulators; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Non-F508del variant; vanzacaftor/tezacaftor/deutivacaftor
    DOI:  https://doi.org/10.1080/25310429.2026.2742057
  41. Int Wound J. 2026 Oct;pii: e71082. [Epub ahead of print]23(10):
    Navigating Treatment Pathways in Diabetic Foot Infection: A Practical Retrospective Analysis of Healing Predictors and the WIfI System.
    Arefeh Tabashiri, Fatemeh Ghodratnia, Pourya Sam Daliri, Ali Farahani, Sepehr Golaghapour Niazi, Homayoun Rezaee, Ilad Alavi Darazam.
      Diabetic foot infection (DFI) is a major cause of lower-extremity amputation. Evidence on optimal management remains inconsistent, and real-world data from multidisciplinary centres are limited. This study describes the characteristics, treatment patterns, and outcomes of patients with DFI at a tertiary referral centre. This retrospective cross-sectional study included all patients with diabetes and confirmed DFI presenting since 2022. Demographic, clinical, laboratory, radiologic, and wound-related data were recorded, and wounds were classified using the Wound, Ischemia, and foot Infection (WIfI) system. Correlation and multiple linear regression analyses identified predictors of healing duration. 69 patients were included (mean age 56.4 ± 13.2 years; 58% male). Most wounds were deep (88.2%); osteomyelitis occurred in 42.2%. Conservative wound care was used in 73.9%, and 79.7% underwent bedside debridement. Minor and major amputation rates were 16.2% and 1.4%. The median healing time was 45 days (interquartile range [IQR] 54), and the mean healing time was 56.0 ± 44.9 days. Healing duration correlated with wound grade, WIfI stage, infection severity, erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, international normalized ratio (INR), wound area, and delay to specialist assessment. Wound grade was the only independent predictor of healing time (β = 0.606, p = 0.001). Limb-preserving management was associated with a low major amputation rate. Wound severity was the strongest determinant of healing duration, underscoring the importance of early referral and structured risk stratification in DFI care.
    Keywords:  diabetic foot; foot ulcer; limb salvage; soft tissue infections; wound healing
    DOI:  https://doi.org/10.1111/iwj.71082
  42. Front Cell Infect Microbiol. 2026 ;16 1971569
    Parvimonas micra and central nervous system infections: mechanisms of transformation from oral commensal to intracranial pathogen and clinical evidence.
    Cancan Gong, Xubo Jing, Shanwei Jiang, Chaoxiao Yu.
      Parvimonas micra (P. micra), an anaerobic oral coccus long dismissed as a culture contaminant, is increasingly recognized as a causative agent of pyogenic central nervous system (CNS) infections, yet its neuropathogenesis remains poorly defined. This narrative review synthesizes 41 peer-reviewed studies identified via a structured comprehensive literature search of PubMed, Embase and Web of Science through June 2026. Epidemiologically, pooling available case reports and small series (n=64 confirmed CNS cases), P. micra is among the most frequently isolated Gram-positive anaerobic cocci in reported brain abscess series, with proportions ranging from approximately 4% to over 10% in individual cohorts; species-level data are inconsistently reported and a precise pooled estimate cannot be derived. A male predominance (approximately 2.7:1) is observed among reported cases, though this should be interpreted cautiously given the small sample size and potential reporting bias. Approximately two-thirds of patients have no documented immunosuppressive condition. Brain abscess represents ~80% of CNS manifestations, with 60-70% presenting as polymicrobial infection. We propose a five-step pathogenic cascade-periodontal dysbiosis, epithelial barrier breach, intravascular survival, blood-brain barrier (BBB) translocation, and intracranial suppuration-as a conceptual framework. Virulence factors including the TmpC-AppA axis and extracellular vesicle DnaK have been characterized in non-CNS models (oral carcinoma, periodontitis, oral lichen planus); their relevance to CNS infection is inferred, and BBB translocation mechanisms remain entirely hypothetical. Metagenomic next-generation sequencing (mNGS) outperforms conventional culture in selected brain abscess cohorts (~85% vs ~50% in pus; ~84% vs ~8% in CSF across CNS infections), though performance varies by specimen type, prior antibiotic exposure, and sequencing platform. All-cause mortality is 5-10% and 20-25% of survivors sustain neurological sequelae, though these estimates may overestimate true population rates due to publication bias. P. micra shows consistently low in vitro minimum inhibitory concentrations to metronidazole and β-lactams. Early empirical anaerobic coverage and consideration of mNGS as a complementary diagnostic tool are recommended for suspected odontogenic brain abscess.
    Keywords:  Parvimonas micra; anaerobe; brain abscess; metagenomic next-generation sequencing; odontogenic infection; pathobiont
    DOI:  https://doi.org/10.3389/fcimb.2026.1971569
  43. Water Res. 2026 Oct 12. pii: S0043-1354(26)01803-8. [Epub ahead of print]309(Pt A): 127132
    Unlocking the PirAB Pandora's box: Genomic epidemiology and phage biocontrol of an emerging waterborne one health crisis.
    Zhiwei Wang, Shihe Zhang, Yubao Li, Shengliang Cao, Xihui Zhu, Ting Yang, Yecheng Wang, Chengrui Zhu, Hui Yan, Duanduan Chen, Huahua Jian.
      Intensive aquaculture promotes the emergence of waterborne pathogens and the accumulation of antimicrobial resistance (AMR), challenging sustainable water management. Acute hepatopancreatic necrosis disease (AHPND), driven by PirAB-producing bacteria, severely threatens crustacean aquaculture. However, the broader environmental distribution of PirAB genes and feasible non-antibiotic control strategies remain insufficiently characterized. Here, we integrated large-scale comparative genomics with experimental phage validation to investigate the dissemination and biocontrol of PirAB-positive (PirAB+) bacteria. Screening 2.37 million bacterial genomes revealed that PirAB homologues span five phyla and 31 genera, extending beyond classical AHPND-associated Vibrio to aquatic, food-associated, and clinical microbiomes. PirAB+ Vibrio strains carried zoonotic virulence markers and elevated AMR burdens, highlighting their potential relevance to public health and water biosecurity. To support biocontrol, we constructed a genomic resource comprising 17,058 phage sequences associated with PirAB+ Vibrio, revealing extensive unexplored viral diversity, broad predicted host interactions, and diverse endolysins. We further isolated 11 phages from aquaculture waters using 55 Vibrio parahaemolyticus strains, selecting two lytic phages for cocktail formulation. In a Cherax quadricarinatus AHPND model, this cocktail achieved 89.3% survival, comparable to florfenicol, while promoting recovery of immune activity and hepatopancreatic tissue integrity. Overall, this study shows that PirAB genes are embedded within a broader network of virulence- and resistance-associated determinants, while providing a genome-guided phage framework for non-antibiotic AHPND control. These findings support phage-based strategies to reduce antibiotic dependence, mitigate AMR selection, and improve aquaculture water biosecurity.
    Keywords:  Acute hepatopancreatic necrosis disease; Antimicrobial resistance; One health; Phage biocontrol; PirAB; Vibrio parahaemolyticus
    DOI:  https://doi.org/10.1016/j.watres.2026.127132
  44. Front Public Health. 2026 ;14 1965508
    From discovery to preparedness: reframing antimicrobial resistance as a global governance challenge.
    Quan Khoi Nguyen, Jeffrey D Mayne, Andrew W Taylor-Robinson.
      Almost a century after the discovery of penicillin, the antimicrobial resistance (AMR) crisis has become as much a failure of global governance as a biomedical challenge. Published Global Burden of Disease estimates for 2000-2021 show a persistent geographic hierarchy of mortality, a pattern consistent with AMR burden being embedded in health system capacity rather than due to pathogen evolution alone. Furthermore, the for-profit pharmaceutical model remains structurally misaligned with the clinical necessity of restricted antibiotic use. This Perspective argues that the next phase of AMR mitigation must pivot from a discovery-dominated paradigm to an integrated preparedness model in which innovation, stewardship, surveillance, and governance are collectively strengthened. We contend that success will be determined less by laboratory and technology breakthroughs than by the political commitment to decouple revenue from sales volume and to govern antimicrobial effectiveness as a shared, exhaustible resource. We propose a coordinated policy toolkit - integrating "push-pull" incentives and One Health surveillance - to protect the epidemiological utility of these finite resources. The antibiotics era began as a story of discovery, became a story of complacency, and must now become a story of stewardship and global governance.
    Keywords:  One Health framework; antibiotic; antimicrobial resistance (AMR); antimicrobial stewardship (AMS); global health governance; infection prevention and control (IPC)
    DOI:  https://doi.org/10.3389/fpubh.2026.1965508
  45. Front Cell Infect Microbiol. 2026 ;16 1981479
    Fusobacterium nucleatum: a keystone bridging pathogen in polymicrobial biofilms and host immune dysregulation.
    Jinwen Sima, Siyu Ji, Guanbao Zhang, Suling Li, Siyu Sun, Wangping Dong, Qiancheng Luo, Qingju Bian, Shuyi Cheng, Yunshuai Wang, Xiaofei Cheng.
      Oral infectious diseases such as periodontitis stem from disrupted homeostasis between host immunity and polymicrobial biofilm communities. Fusobacterium nucleatum, a ubiquitous oral commensal, is a key intermediate colonizer with well-documented interspecies coaggregation activity. It has been proposed as a bridging pathobiont that contributes to microbial dysbiosis and immune dysregulation at the host-microbe interface, though its in vivo structural bridging function remains debated. This mini-review synthesizes recent advances in understanding the dual functions of F. nucleatum in interspecies microbial interactions and host pathogenic crosstalk. We first delineate the molecular basis of its structural bridging role, focusing on surface adhesins FadA and Fap2 that mediate interspecies coaggregation, support colonization by late-periodontopathogens such as Porphyromonas gingivalis, and enable epithelial barrier invasion. We then dissect mechanisms by which F. nucleatum modulates innate and adaptive immune responses, propagating chronic inflammatory tissue damage while subverting host clearance pathways. Furthermore, we discuss synergistic pathogenicity with co-occurring pathogens and the systemic implications of disseminated F. nucleatum in extraoral disorders including colorectal cancer and adverse pregnancy outcomes. Finally, we highlight the translational promise of targeting F. nucleatum-mediated adhesion and immunomodulation as an ecological therapeutic strategy for oral infections and their systemic sequelae.
    Keywords:  Fusobacterium nucleatum; colorectal cancer; immune dysregulation; periodontitis; polymicrobial biofilms
    DOI:  https://doi.org/10.3389/fcimb.2026.1981479
  46. Nat Struct Mol Biol. 2026 Oct 21.
    Molecular control of bacterial immunity.
    Landon John Getz, Sam R Fairburn, Karen Lee Maxwell.
      Phage infection places strong selective pressure on bacteria to mount a rapid immune response to ensure survival. Although recent studies have uncovered a wide diversity of bacterial immune systems, how these systems function under the tight time constraints of phage infection remains poorly understood. Here we summarize structural, biochemical and genetic insights into bacterial immunity, focusing on steps that link infection sensing to activation and effector function. We highlight how conformational change, protein assembly and spatial organization shape immune activation, and how phages employ counter-defense strategies that disrupt these processes.
    DOI:  https://doi.org/10.1038/s41594-026-01901-9
  47. Microbiol Resour Announc. 2026 Oct 19. e0083326
    Draft genome sequences for six Staphylococcus aureus isolates from cystic fibrosis patients in Oklahoma.
    Rebecca Wilson, Noopur Dasgupta, Chelsea L Murphy, William C Starr, Kaylea M Feldman, Elizabeth Pascual, Erika I Lutter.
      Staphylococcus aureus causes many infections and can be life-threatening when present in the lungs of patients with cystic fibrosis (CF). To expand the current knowledge of S. aureus infections in CF lung diseases, we report the genomes of six S. aureus strains isolated from cystic fibrosis patients in Oklahoma, USA.
    Keywords:  Staphylococcus aureus; cystic fibrosis; genomes
    DOI:  https://doi.org/10.1128/mra.00833-26
  48. Am J Reprod Immunol. 2026 Oct;96(4): e70337
    Beyond the Silent Endometrium: Dysbiosis, Immune Subversion and Antimicrobial Resistance in Chronic Endometritis: A Narrative Review.
    Ahmed Wael Moftah.
      Chronic endometritis (CE) represents an insidious and frequently underdiagnosed inflammatory condition of the endometrial stroma, increasingly recognized as a principal contributor to unexplained infertility, recurrent implantation failure and recurrent pregnancy loss. Historically relegated to a histological curiosity, CE has been reframed as a biologically complex disorder characterized by the convergence of endometrial microbial dysbiosis, immunological subversion, and, increasingly, antimicrobial resistance (AMR). This narrative review synthesizes contemporary evidence examining the mechanistic interplay between aberrant endometrial microbiota composition, disrupted innate and adaptive immune responses, and the emergence of antibiotic-resistant endometrial pathogens, collectively undermining endometrial receptivity and embryo implantation. We critically appraise the diagnostic limitations inherent to current histological and microbiological standards, and examine the translational implications of next-generation sequencing for the characterization of the endometrial microbiome. Furthermore, we interrogate the therapeutic paradox posed by AMR in clinical CE management, and delineate future research trajectories encompassing microbiome-targeted therapeutics, immunomodulatory strategies, and the ethical dimensions of emerging diagnostic and treatment frameworks. A convergent pathophysiological model is proposed in which microbial dysbiosis, immune dysregulation, and AMR form a self-reinforcing axis of reproductive failure, demanding integrated diagnostic and therapeutic paradigms.
    Keywords:  antimicrobial resistance; chronic endometritis; endometrial dysbiosis; endometrial microbiome; immune subversion; recurrent implantation failure; reproductive failure
    DOI:  https://doi.org/10.1111/aji.70337
  49. Int J Infect Dis. 2026 Oct 17. pii: S1201-9712(26)00828-3. [Epub ahead of print] 109193
    Repeat antimicrobial susceptibility testing of serial bacterial isolates: clinical utility and diagnostic stewardship.
    Tokeshwar Kumar Sahu, Pravin Gadkari, Jaishriram Rathored.
       OBJECTIVES: To synthesize evidence on the interpretation and temporal stability of antimicrobial susceptibility profiles in serial bacterial isolates and to identify factors that inform repeat testing within diagnostic stewardship.
    METHODS: This narrative review integrates evidence from studies of serial clinical isolates with data on analytical variability, within-host resistance evolution, heteroresistance, antimicrobial exposure, and diagnostic stewardship.
    RESULTS: Susceptibility profiles are generally stable over short intervals, although clinically relevant changes vary according to bacterial species, antimicrobial agent, specimen context, and elapsed time. Small MIC shifts, particularly near clinical breakpoints, may result in categorical discordance without indicating true resistance emergence. Pseudomonas aeruginosa exhibits greater short-term phenotypic variability than several other common pathogens. Repeat AST is most strongly supported when infection persists or recurs, the clinical response is inadequate, antimicrobial exposure may have selected for resistance, or the consequences of missed resistance are substantial. In selected lower-risk settings, referral to a recent susceptibility result may be appropriate, provided that laboratory and clinical override mechanisms remain available.
    CONCLUSIONS: Short-term susceptibility stability may support conservative referral to a recent AST result, but the degree of instability varies by organism, antimicrobial agent, and specimen context. Where a single operational interval is required, laboratories may adopt the shortest interval supported by local or otherwise applicable evidence, with predefined overrides for higher-risk clinical situations. Prospective multicentre validation is required before specific intervals can be generalized across clinical and laboratory settings.
    Keywords:  Antimicrobial resistance; Antimicrobial susceptibility testing; Diagnostic stewardship; Serial bacterial isolate; Susceptibility profile
    DOI:  https://doi.org/10.1016/j.ijid.2026.109193
  50. Hlife. 2026 Sep;4(9): 554-557
    Establishing a regulatory framework for phage therapy in China.
    Jixin Yang, Haiyan Chen, Xuesong He, Nannan Wu, Shuai Le, Tongyu Zhu.
      
    DOI:  https://doi.org/10.1016/j.hlife.2026.05.001
  51. Eur J Pediatr. 2026 Oct 23. pii: 878. [Epub ahead of print]185(11):
    Targeting the gut-liver axis and gut microbiome in pediatric metabolic dysfunction-associated steatotic liver disease: current evidence and future directions.
    Vybhav Venkatesh, Toshifumi Yodoshi, Keerthivasan Seetharaman, Neha Anushree.
      Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children, closely linked to the rising prevalence of childhood obesity and metabolic syndrome. Increasing evidence highlights the central role of the gut-liver axis and the gut microbiome in disease pathogenesis, offering potential targets for therapeutic modulation. This review aims to summarize current evidence on interventions targeting the gut-liver axis and the gut microbiome in pediatric MASLD and explore emerging strategies in this field. This narrative review was undertaken after searching PubMed and Embase databases for available up-to-date literature on pediatric MASLD and therapeutic interventions targeting the gut microbiome and gut-liver axis, including dietary therapy, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and pharmacological therapies. Dietary interventions, including low-free-sugar and Mediterranean-style diets, improve hepatic and metabolic outcomes, although microbiome-mediated benefits remain unproven in children. Probiotics and synbiotics show modest and variable effects, with heterogeneity in strains, dosing, and outcomes limiting definitive conclusions. Evidence for FMT in pediatric MASLD is absent, with only indirect evidence from adolescent obesity and other pediatric diseases. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and farnesoid X receptor agonists, have demonstrated metabolic and hepatic benefits primarily in adult populations, while effects on microbial metabolism, intestinal barrier integrity, and bile acid signalling provide potential mechanisms linking these therapies to the gut-liver axis. Although microbiome-mediated mechanisms have been proposed, direct evidence linking these therapies to microbiome changes in pediatric MASLD is currently lacking. Emerging approaches such as precision nutrition, engineered probiotics, and bacteriophage therapy offer potential avenues for targeted modulation of disease-relevant pathways.
    CONCLUSION:   Therapeutic modulation of the gut-liver axis and the gut microbiome represents a biologically plausible and evolving strategy in pediatric MASLD. Current pediatric evidence remains limited, and robust, well-designed clinical trials incorporating microbiome profiling and clinically meaningful endpoints are needed to establish efficacy and enable personalized, therapeutic strategies.
    WHAT IS KNOWN: • Pediatric MASLD is increasing in prevalence, and alterations in the gut-liver axis and the gut microbiome are known to contribute to the pathogenesis of the disease by influencing various disease-relevant pathways such as intestinal permeability, bile acid signaling, hepatic lipid metabolism, inflammation, and fibrogenesis.
    WHAT IS NEW: • This review provides current evidence for interventions targeting the gut microbiome and gut-liver axis in pediatric MASLD including dietary modulation, probiotics, and pharmacological interventions and highlights new approaches such as precision nutrition, engineered probiotics, bacteriophage therapy, and personalized treatment strategies.
    Keywords:  Diet; Gut microbiome; Gut-liver axis; Metabolic dysfunction–associated steatotic liver disease; Probiotics
    DOI:  https://doi.org/10.1007/s00431-026-07548-4
  52. J Clin Epidemiol. 2026 Oct 20. pii: S0895-4356(26)00448-8. [Epub ahead of print] 112572
    When Clinical Prediction Models Meet Clinical Judgment: A Framework for Classifying Prediction Approaches.
    Felix Kerscher, Ilse P Peringa, Eline G M Cox, Marvin Neumann, Iwan C C van der Horst, Rob R Meijer, Jacqueline Koeze.
       BACKGROUND AND OBJECTIVE: There is an ever increasing interest in using clinical prediction models to improve diagnostic and prognostic accuracy. However, the literature often conflates distinct prediction approaches, resulting in ambiguous findings and slowing scientific progress. This commentary aims to clarify the various ways in which physicians use clinical prediction models and highlight the implications of these approaches for prediction accuracy by drawing on an existing framework from the judgment and decision-making literature.
    METHODS: We promote a framework distinguishing between four distinct prediction approaches: clinical judgment, mechanical judgment, clinical synthesis, and mechanical synthesis. We apply this framework to recent studies and illustrate how it distinguishes between previously conflated approaches.
    RESULTS: Our analysis demonstrates that current research often obscures meaningful differences between the prediction approaches, thereby impeding improvement in patient care. The framework provides conceptual clarity and highlights clinical synthesis, in which the physician incorporates the model output into their own judgment, as a practical yet under-researched approach.
    CONCLUSIONS: The prediction accuracy achieved in practice depends on how physicians use clinical prediction models. Greater recognition and use of the proposed framework can improve future research by properly classifying prediction approaches, fostering more accurate research syntheses, and supporting the more effective and fair application of clinical prediction models in practice.
    Keywords:  clinical judgment; clinical prediction models; clinical synthesis; decision-making; framework; prediction accuracy
    DOI:  https://doi.org/10.1016/j.jclinepi.2026.112572
  53. Respir Res. 2026 Jul 23. pii: 412. [Epub ahead of print]27(1):
    Electrical impedance tomography in neonatal respiratory diseases: a clinical review of applications and evidence.
    Yifan Wang, Yaping Song, Caiju Xing, Feng Fu, Xun Jiang, Yan Lin.
      Neonatal respiratory diseases remain a leading cause of morbidity and mortality in intensive care settings, with management complicated by the limitations of current monitoring tools. Chest radiography provides only static snapshots and cannot capture the dynamic evolution of lung aeration, while lung ultrasound, though portable, remains operator-dependent and incapable of quantifying regional ventilation. Electrical Impedance Tomography (EIT) has emerged as a noninvasive, radiation free imaging modality that addresses these gaps by enabling real time, continuous visualization of regional lung function at the bedside. This review synthesises evidence from studies published between 2011 and 2026, examining how EIT informs the management of neonatal respiratory distress syndrome, acute respiratory distress syndrome, bronchopulmonary dysplasia, pneumothorax, and the transitions inherent to mechanical ventilation. Across these disease contexts, EIT reveals regional ventilation heterogeneity invisible to conventional monitors, provides immediate physiological feedback during therapeutic interventions, and enables early detection of complications before clinical deterioration. We identify key barriers to clinical adoption, including technical limitations, lack of standardised protocols, and the need for outcome driven trials, and propose a research agenda to accelerate translation. By reframing EIT not merely as an imaging tool but as a dynamic decision support system integrated into clinical workflows, we aim to provide clinicians with a framework for leveraging this technology to improve outcomes in the most vulnerable patients.
    Keywords:  Electrical impedance tomography; Neonate; Pulmonary impedance; Respiratory diseases
    DOI:  https://doi.org/10.1186/s12931-026-03838-5
  54. BMC Infect Dis. 2026 Jul 28. pii: 1872. [Epub ahead of print]26(1):
    Global gram-negative diabetic foot infection prevalence and its associations with climate: a systematic review and meta-analysis.
    Marcos C Schechter, Ben Rabin, Ellen Martinson, Mia S White, Baffour Otchere, J Raymond, Jillian Dunbar, Meg McAloon, Priyanka A Bhanushali, Kyra L Urquhart-Foster, Maya Fayfman, Mohammed K Ali, Eric Senneville, Rodrigo M Carrillo-Larco, Sophie Lockwood.
       BACKGROUND: The International Working Group on the Diabetic Foot guidelines state that Pseudomonas aeruginosa and overall gram-negative diabetic foot infections (psaDFI and gnDFI) are more common in tropical and subtropical zones vs. temperate zones, and in North Africa/Asia vs. Western Europe/North America based on non-systematic comparisons of cohort studies.
    METHODS: We performed a systematic review and meta-analysis of studies of any design and language published between January 1, 2010, and December 15, 2020, that reported the proportion of participants with DFIs and microbiological tests that were positive or negative for Pseudomonas aeruginosa and/or gram-negatives of any species. We calculated the pooled prevalence of psaDFIs and gnDFIs using random effects models.
    RESULTS: We identified 246 studies (36,788 participants) reporting on psaDFI prevalence and 55 studies (6,079 participants) reporting on gnDFI prevalence. The psaDFI pooled prevalence in tropical, subtropical, and temperate zones was 19% (95%CI 17-22%), 14% (95%CI 12-17%), and 14% (95%CI 11-17%), respectively. The gnDFI pooled prevalence in tropical, subtropical, and temperate zones was 68% (95%CI 61-74%), 54% (95%CI 45-63%), and 43% (95%CI 35-52%), respectively. The pooled prevalence of psaDFIs and gnDFIs was higher in studies conducted in Asia/North Africa [psaDFI 18% (95%CI 16-20%) and gnDFI 57% (95%CI 51-64%)] compared to studies conducted in North America/Western Europe [psaDFI 12% (95%CI 9-16%) and gnDFI 42% (95%CI 32-52%)]. However, the pooled prevalences of these infections were similar in temperate zones of these regions. Few studies reported data on key risk factors for psaDFIs and gnDFIs, including DFI severity (53%) and prior antibiotic exposure (91%), and there was substantial between-study heterogeneity within climate zones and regions.
    CONCLUSIONS: This meta-analysis indicates psaDFIs and gnDFIs may be more prevalent in tropical zones compared to temperate zones and suggests solar climate zones provide additional nuance compared to the guideline-proposed broad regional groupings. However, available studies lack necessary data to separate the effects of climate and location from other risk factors for psaDFIs and gnDFIs. Our findings cannot establish causality between solar climates, regions, and DFI microbiology.
    REGISTRATION: PROSPERO CRD42022279019.
    Keywords:  Climate; Diabetic foot; Microbiology
    DOI:  https://doi.org/10.1186/s12879-026-13916-0
  55. Explor Res Clin Soc Pharm. 2026 Dec;24 100852
    Artificial intelligence in pharmacy and pharmaceutical sciences: Research output, trends, and thematic priorities - A descriptive analysis of web of science-indexed publications (2010-2025).
    Bushra Salman, Amna Mohamed, Asim Jamal Shaikh, Anwar Al-Mahrizi, Roula Al-Shidi, Suhaila Al-Farsi, Nariman Hashish, Zayana Al-Kiyumi, Omar Ayaad, Khalid Al-Baimani.
       Background: Artificial intelligence (AI) is rapidly transforming pharmacy and pharmaceutical sciences (PPS), yet the evolution, research priorities, and global landscape of AI-related research within this field have not been comprehensively characterized.
    Methods: A descriptive bibliometric analysis of publications indexed in the Web of Science Core Collection was conducted for studies published between 2010 and November 9, 2025. Publication trends, document characteristics, journals, publishers, countries, authors, research themes, citation impact, and funding organizations were analyzed using descriptive statistics, keyword analysis, and descriptive network visualization.
    Results: A total of 9671 publications were identified. Research output increased markedly over the study period, with publications from 2020 onward accounting for 84.9% of the literature. Original research articles published in English predominated. The Journal of Chemical Information and Modeling, Journal of Pharmaceutical Sciences, and Briefings in Bioinformatics were the leading publication venues. China, India, and South Korea were the most productive countries based on corresponding author affiliation. Drug Design and Modeling was the predominant thematic domain, encompassing 42.1% of publications, whereas Clinical Pharmacology and Precision Therapeutics represented 3.6%. Pharmacy Operations and Clinical Decision Support (1.6%), Pharmacovigilance and Medication Safety (1.2%), Clinical Trials and Drug Development (0.6%), and Pharmaceutical Manufacturing and Supply Chain Management (0.5%) were comparatively underrepresented. Citation analysis indicated that the most influential publications were primarily methodological AI studies rather than pharmacy-specific applications.
    Conclusions: AI-related research in PPS has expanded rapidly but remains predominantly focused on computational drug discovery and preclinical applications. Greater emphasis on clinical implementation, patient-centered pharmacy practice, pharmacovigilance, and broader geographic participation is needed to support equitable translation of AI into pharmaceutical care.
    Keywords:  Artificial intelligence; Bibliometric analysis; Bibliometrics; Drug discovery; Machine learning; Pharmaceutical sciences; Pharmacy; Publication trends; Web of science
    DOI:  https://doi.org/10.1016/j.rcsop.2026.100852
  56. Eur J Pharm Sci. 2026 Oct 22. pii: S0928-0987(26)00267-8. [Epub ahead of print] 107693
    Multimodal Deep Learning for Wound Healing Prediction.
    Tatu Rojalin, Aleksi Kröger, Elle Koivunotko, Benjamin Pörhö, Timo Laaksonen, Jouni Partanen, Chris Pridgeon, Mari Madetoja, Antti Airola, Jan Akmal, Marjo Yliperttula.
      Chronic wounds, particularly diabetic foot ulcers, heal unpredictably and impose substantial healthcare costs. Deep learning (DL) systems that integrate complementary data streams could support preclinical studies by assessing wound status and therapy efficacy reliably in small-n studies. We developed a three-branch neural network combining convolutional feature extraction for red-green-blue (RGB) images, infrared thermography, and wound-area measurements to classify healing stage and infer treatment response in diabetic mouse wound model. In descriptive ablation analysis, the model integrating RGB and wound-size inputs achieved higher accuracy than the RGB-only configuration (0.75 vs. 0.70), suggesting that explicit size context provided useful complementary information. Thermal images appeared qualitatively informative during early healing but contributed limited additional signal later, likely reflecting subtle inflammatory gradients or angiogenesis in healthy murine skin; this observation motivated a constrained weighted-fusion strategy. In the development-stage comparison, static fusion with tunable fixed weights yielded the highest observed performance (∼0.85 accuracy on the development test subject). Grad-CAM visualizations showed that predictions arose from biologically relevant regions rather than image artifacts. Experiments without subject-level partitioning produced inflated metrics, underscoring the need for grouping by subject to ensure generalizable evaluation. Nested Leave-One-Group-Out cross-validation with KerasTuner-based hyperparameter tuning yielded a mean accuracy of 0.71, estimating performance on unseen subjects. This resulting proof-of-concept model predicts treatment responses for wounds treated with nanofibrillated-cellulose hydrogel. Multimodal DL combining standard and thermal photography with size metrics can stage wound healing and detect divergent treatment trajectories and thus be used in preclinical efficacy evaluation of novel wound treatments. With larger, clinically annotated datasets, this approach could be applied in a clinical setting as well.
    Keywords:  AI; Biomedical Imaging; Deep Learning; Diabetic Wound; Hydrogel; Nanofibrillated Cellulose
    DOI:  https://doi.org/10.1016/j.ejps.2026.107693
  57. iScience. 2026 Nov 20. 29(11): 117156
    Harnessing hydrogel technology for advanced periodontitis therapy: A multifunctional approach to oral health restoration.
    Xiaoqing Zhuo, Shaoqiang Wang, Li-Yuan Liu, Minmin Zhu, Zhenjiang Zhang, Yuqi Zhou, Maoshan Wang, Xudong Deng, Yanxia Miao, Niannian Li, Xue-Ting Wang, Hongguang Zhu.
      Periodontitis is a bacterially driven inflammatory disease that can lead to tooth mobility and tooth loss. Conventional non-surgical therapy, antibiotics, and surgery may be limited by residual subgingival biofilms, antimicrobial resistance, and variable clinical outcomes. This review synthesizes recent studies of hydrogel-based systems for local periodontal therapy, focusing on stimuli-responsive release mechanisms, cargo-loading approaches, and regenerative outcomes in relevant animal models. Across these studies, hydrogels function as localized delivery matrices that can prolong retention at periodontal defects, regulate therapeutic exposure, and support tissue repair. We further evaluate translational considerations, including degradation behavior, long-term in vivo stability, and immunocompatibility. These findings position hydrogels as adaptable platforms for more precise periodontitis management and identify priorities for preclinical optimization before clinical translation.
    Keywords:  anti-inflammatory; antibacterial; bioactive materials; clinical translation; drug delivery; hydrogel; minimally invasive therapy; periodontitis; stimuli-responsive hydrogel; tissue regeneration
    DOI:  https://doi.org/10.1016/j.isci.2026.117156
  58. Front Immunol. 2026 ;17 1957346
    Biofilm-host immunometabolic crosstalk in Staphylococcus aureus orthopedic implant infection: mechanisms and translational constraints.
    Jixin Chen, Qinxin Zhou, Dongdong Cao, Weijie Yu, Yongming Zhang, Jianliang Chen, Xiaodong Zheng, Feng Ye.
      Orthopedic implant biofilms are not only antibiotic-tolerant bacterial communities but metabolically active niches that reshape host immunity. Compared with planktonic infection, mature biofilms impose spatial and metabolic constraints that can uncouple leukocyte recruitment from sterilizing activity. Neutrophils can penetrate and phagocytose portions of Staphylococcus aureus biofilms, but clearance becomes incomplete as biofilms mature and may coexist with degranulation and neutrophil extracellular trap-associated tissue injury. Macrophages show impaired access and bactericidal programming, and biofilm-derived lactate can promote interleukin-10 (IL-10) through histone deacetylase 11 (HDAC11)/HDAC6-dependent epigenetic reprogramming in experimental systems. Human periprosthetic joint infection (PJI) tissues are enriched in granulocytic myeloid-derived suppressor cells (G-MDSCs), whereas the glycolysis/hypoxia-inducible factor 1-alpha (HIF-1alpha) phenotype and its contribution to persistence are supported primarily by murine PJI, with limited human transcriptomic corroboration. In chronic S. aureus infection models, MDSC-derived lactate can suppress CD4-positive (CD4+) T-cell glycolysis; conversely, immune pressure drives heterogeneous bacterial metabolic, stress-response, and virulence programs. We synthesize these interactions as bidirectional biofilm-host immunometabolic crosstalk linking persistent infection to bone-interface damage. Source control and antibiotics remain essential. Local, time-limited, dysfunction-directed host interventions are presented here as a hypothesis-generating translational framework rather than evidence-based clinical recommendations, because host-directed immunometabolic therapies for PJI remain preclinical.
    Keywords:  Staphylococcus aureus; biofilm; immunometabolism; macrophages; myeloid-derived suppressor cells; neutrophils (PMNs); orthopedic implant infection
    DOI:  https://doi.org/10.3389/fimmu.2026.1957346
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