bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–09–27
53 papers selected by
Luca Bolliger, lxBio
  1. A Rapid Screening Strategy for Secondary Bacteriophages to Counter Phage Resistance in Carbapenem-Resistant Acinetobacter baumannii.
  2. The Therapeutic Potential of Phages in Multi-Drug Resistance Infections and Future Directions.
  3. Novel biofilm-targeted therapeutics for oral infections: enzymes, EPS disruptors, phage/CRISPR, photodynamic and cold-plasma approaches - a systematic review.
  4. Phages Targeting Flagella: Adsorption and Infection Mechanisms of Flagellotropic Phages.
  5. Bacteriophage-bacteria coevolution: from molecular arms races to ecological and applied perspectives.
  6. A consensus-based guideline for personalized bacteriophage therapy.
  7. The Wound-Heart Axis: Can Chronic Wounds Contribute to Cardiac Dysfunction?
  8. From laboratory to clinical application: a narrative review of bacteriophage therapy for antimicrobial-resistant infections in veterinary medicine.
  9. Rational Design of a Phage Cocktail for Effective Control of Multidrug-Resistant Uropathogenic Escherichia coli from Hospitalized Patients.
  10. Urinary Tract Infections: Molecular Determinants of Uropathogenicity and Their Translation into Contemporary Clinical Practice.
  11. Bridging the gap between experimental evidence and clinical applications of antipseudomonal phage therapy against Pseudomonas aeruginosa.
  12. Precision phage therapy in the AI/ML era: a systematic review of discovery-to-clinical translation evidence.
  13. Mapping Bacteriophage-Based Antimicrobial Research in Southeast Asia: A Bibliometric Analysis of Scientific Productivity, Knowledge Structure, and Emerging Research Pathways.
  14. Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance.
  15. Artificial Intelligence and Bioengineering Approaches for Antimicrobial Resistance Prediction.
  16. Genomic and functional characterization of six novel phages targeting multidrug-resistant Escherichia coli: promising candidates for clinical phage therapy.
  17. The Human Vaginal Virome: Composition, Microbiome Interactions, and Implications for Bacterial Vaginosis, HPV Persistence, and Preterm Birth.
  18. Microbial allies in malignancy: Role of Porphyromonas gingivalis and Candida biofilms in oral squamous cell carcinoma.
  19. Non-antibiotic therapeutic approaches for antimicrobial resistance: current evidence and future directions.
  20. Inflammasome-derived biomarkers in wound healing: linking tissue repair, chronic inflammation, fibrosis, and precision therapeutics.
  21. Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical Pipeline.
  22. Lytic bacteriophages targeting carbapenem-resistant Klebsiella pneumoniae isolated in a resource-limited Zambian laboratory.
  23. Phage Genomics and Bioinformatics in Therapeutic Development: Evidence Limits, Validation Gates, and Translational Decision-Making.
  24. Biofilm Dynamics and Antimicrobial Resistance in Rabbit Odontogenic Infections: A One Health Perspective.
  25. Biofilms and beyond: The impact of Porphyromonas gingivalis on oral squamous cell carcinoma.
  26. Innovative Applications of Artificial Intelligence in Bacteriophage Research: A New Chapter in Future Medicine.
  27. Vitamins and Chronic Wounds: How Altered Pharmacokinetics and Comorbidities Contribute to Vitamin Deficiencies.
  28. Novel options for the management of C. difficile: a look into the future.
  29. Phage-Antibiotic-Peptide Synergy Overcomes Biofilm-Mediated Multidrug Resistance in Serratia marcescens.
  30. The Role of Infrared Thermography in the Diagnosis and Monitoring of Diabetic Foot Infection: A Systematic Review.
  31. Animal-Derived Antimicrobial Peptides: Emerging Therapeutic Strategies against Multidrug-Resistant Pathogens.
  32. Antimicrobial Strategies for Chronic Cutaneous Ulcers: From Preclinical Nanotechnology to Clinical Practice.
  33. International epidemiology of antimicrobial resistance in people living with chronic lung infection.
  34. Modeling Phage-Antibiotic Synergy, Innate Immunity, and Phage Resistance in Multidrug-Resistant Acinetobacter baumannii.
  35. Isolation and Genomic Characterisation of Five Novel Lytic Bacteriophages Infecting the Emerging Pathogen Klebsiella grimontii.
  36. Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ.
  37. Deciphering the modular structure of phage depolymerase: a dual-action strategy for biofilm degradation and targeted Pseudomonas aeruginosa binding.
  38. Albumin Hydrogels Loading Bacteriophage PA57 as a Promising Platform for Pseudomonas aeruginosa Infection Management.
  39. Non-Battle Injury in Military Operations Novel Treatment for Soft Tissue Injury and Infection with Logistics Implications.
  40. Neglected ESKAPE Pathogens in Companion Animals: Diagnostic Bias, Zoonotic Blind Spots, and Phytotherapeutic Opportunities.
  41. Receptor Structure Shapes Host Range but Incompletely Predicts High Activity in Klebsiella pneumoniae Phage Cocktails.
  42. Diabetic Foot Ulcer-Associated Versus Other Lower-Extremity Necrotising Soft-Tissue Infections: A Retrospective Cohort Study.
  43. Hydrogels for Local Drug Delivery in Biofilm-Associated Periprosthetic Joint Infection: Current Progress and Future Directions.
  44. Multidrug-Resistant Organisms in Combat-Related Injuries: Insights from Iraq, Afghanistan, Ukraine, and Implications for Large-Scale Combat Operations.
  45. Artificial intelligence applications in biofilm research: computational approaches for biofilm analysis and antimicrobial prediction.
  46. Revascularization Gaps in Diabetic Foot Disease in Nigeria: Health-System Constraints and the Need for a National Limb-Salvage Strategy.
  47. The Oral and Nasal Gateway Microbiomes: Salivaomics and Systemic Health at the Airway-Digestive Interface.
  48. Bacteriophages 6phi8, 6phi10, and 6phi13 Isolated from the Therapeutic Cocktail "Sextaphag®".
  49. Periodontitis and Alzheimer's disease, common pathways in down syndrome.
  50. Bacteriophages and polymeric delivery systems: a mapping review.
  51. Metallo-β-lactamase-producing Pseudomonas aeruginosa: epidemiology, diagnostic challenges and therapeutic strategies in the era of MDR/XDR resistance.
  52. Antibiotic-Free Strategies for Managing Antimicrobial-Resistant Infections.
  53. A Biological Approach to Antimicrobial Resistance in New and Old Bacterial Pathogens.
  1. Antibiotics (Basel). 2026 Sep 04. pii: 864. [Epub ahead of print]15(9):
    A Rapid Screening Strategy for Secondary Bacteriophages to Counter Phage Resistance in Carbapenem-Resistant Acinetobacter baumannii.
    Ruei-Sen Jiang, Li-Kuang Chen, Chun-Chieh Tseng.
      Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major nosocomial pathogen; bacteriophage therapy is a promising alternative, but its principal challenge is the rapid emergence of phage resistance. Cocktails counter this yet they are usually assembled by simply pooling phages active against the bacterium, not designed against the resistant mutants that arise. Methods: Next evolutionary phage typing (NEPT) addresses this by inducing resistance to a primary phage and then selecting secondary phages that lyse the resulting resistant mutant. Because choosing effective secondary phages still relies on qualitative visual reading of plaques (size and clarity), this study aimed to identify a rapid quantitative criterion. Results: Using the clinical strain CRAB 43895 and primary phage ϕ8, we obtained 65 NEPT-derived secondary phages that lyse the ϕ8-resistant mutant (ϕ8R) and combined four quantitative indicators-relative bacterial growth, lytic capability, coverage rate, and plaque morphology-with binary logistic regression to predict effective inhibition by the ϕ8 + secondary-phage cocktail (96-h OD600 < 0.1). Of the four, only lytic capability (the titer after 3 h of co-culture) independently predicted effective inhibition (ROC AUC = 0.76; at ≥107 plaque-forming units (PFU)/mL, sensitivity 0.83, specificity 0.69). Conclusions: Lytic capability thus provides a rapid (~8-12 h), quantitative criterion for selecting effective secondary phages within the NEPT framework, improving on conventional qualitative typing.
    Keywords:  Acinetobacter baumannii; next evolutionary phage typing; phage cocktail; phage resistance; secondary phage
    DOI:  https://doi.org/10.3390/antibiotics15090864
  2. Viruses. 2026 Aug 27. pii: 937. [Epub ahead of print]18(9):
    The Therapeutic Potential of Phages in Multi-Drug Resistance Infections and Future Directions.
    Shengting Zhang, Huili Tao, Sha Zhao, Yunlin Wei.
      Phage therapy has been revisited as a biologically based strategy to tackle the escalating global crisis of multidrug-resistant (MDR) bacterial infections. Distinct from conventional antibiotics, bacteriophages target specific bacterial strains precisely, replicate locally at infection sites, penetrate bacterial biofilms, and exert synergistic effects with multiple antimicrobial agents. These inherent mechanistic advantages minimize collateral damage to the host's commensal microbiota. However, existing regulatory frameworks-originally established for chemically synthesized, mass-produced drugs-fail to accommodate personalized, living biological phage products, leading to uncertain approval pathways and inconsistent manufacturing supervision. Clinical experience of phage therapy is predominantly derived from compassionate-use cases via multiple administration routes, including intravenous, inhaled, and topical delivery. This review systematically analyzes major challenges restricting clinical application, such as standardized production, quality control, pharmacokinetic characterization, rapid pathogen identification, and regulatory adaptation, as well as the limited performance of fixed phage cocktails against genetically heterogeneous bacterial populations. Current clinical practice demonstrates that phage therapy exhibits acceptable safety profiles across intravenous, inhaled, and topical administration routes, with promising therapeutic outcomes in otherwise untreatable MDR infections. Nevertheless, stable and reproducible clinical outcomes are hindered by multiple scientific and operational obstacles: the absence of unified standards for phage production and quality control, insufficient understanding of route-dependent pharmacokinetics, the imperative demand for rapid pathogen identification to enable precise phage matching, and the limited efficacy of fixed-cocktail regimens against genetically diverse clinical isolates. The successful integration of phage therapy into routine clinical practice relies on coordinated progress in diagnostic infrastructure construction, GMP-compliant phage repository establishment, international regulatory harmonization, and high-quality evidence generation through well-designed clinical trials. Rather than serving as a universal substitute for antibiotics, phage therapy is best implemented as a precision complementary component within comprehensive antimicrobial stewardship strategies.
    Keywords:  antimicrobial resistance; personalized biologics; phage therapy; phage–antibiotic synergy; precision anti-infectives; regulatory science
    DOI:  https://doi.org/10.3390/v18090937
  3. Front Cell Infect Microbiol. 2026 ;16 1915920
    Novel biofilm-targeted therapeutics for oral infections: enzymes, EPS disruptors, phage/CRISPR, photodynamic and cold-plasma approaches - a systematic review.
    Prabhu Manickam Natarajan, Vijay Ebenezer, Sudhir Rama Varma, Pradeepa Ganesh.
       Background: Microbial biofilms underpin the chronicity, recurrence and antimicrobial tolerance of most oral infections. As mechanical and antibiotic strategies are constrained by antimicrobial resistance and by the protective biofilm matrix, non-antibiotic, biofilm-targeted therapeutics have attracted intense interest. We systematically mapped and appraised five mechanistically distinct modalities - matrix-degrading (anti-biofilm) enzymes, extracellular polymeric substance (EPS) disruptors, bacteriophage and CRISPR-based therapy, antimicrobial photodynamic therapy (aPDT) and cold atmospheric plasma (CAP) - selected because each targets a different, non-antibiotic vulnerability of the biofilm.
    Methods: Following a PRISMA 2020 protocol (PROSPERO), PubMed, Embase, Web of Science and Scopus were searched from inception to January 2026. In vitro, animal and clinical studies reporting a quantitative anti-biofilm outcome for any modality against oral or oral-relevant pathogens were included, appraised with RoB 2, SYRCLE and a modified in vitro checklist, and the certainty of evidence rated with GRADE. Prespecified subgroup (biofilm maturity, species complexity) and quality-based sensitivity analyses were performed.
    Results: Seventy-eight studies met the criteria; 58% (45/78) were in vitro/ex vivo, 16 animal and only 17 (22%) clinical, so clinical evidence was limited and concentrated in aPDT. aPDT provided small but consistent adjunctive gains over scaling and root planing (SRP): pooled additional probing-pocket-depth reduction ≈0.35-0.45 mm and clinical-attachment gain ≈0.25-0.34 mm at 3-6 months (low-moderate certainty). EPS disruptors reduced biofilm biomass by 58-94% and CAP rendered ≈90% of treated samples culture-negative in vitro, but both rested on preclinical data (low-very-low certainty). Enzymes and phage/CRISPR acted mainly by dispersal or targeted killing (representative reductions ≈1.5-4.5 log10 CFU). Efficacy fell consistently against mature, multispecies biofilms; sensitivity analysis excluding high-risk studies changed estimates minimally.
    Conclusion: On current evidence these modalities are best positioned as adjuncts that enhance, rather than replace, mechanical and antimicrobial therapy. Only aPDT currently has sufficient clinical evidence for consideration as an adjunct to conventional therapy; the remaining modalities remain investigational and require further translational and clinical development. Combination (matrix-first) strategies, targeted delivery, and standardised oral-biofilm models and clinical trials are priorities.
    Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261428848.
    Keywords:  CRISPR; anti-biofilm enzymes; antimicrobial photodynamic therapy; antimicrobial resistance; bacteriophage therapy; cold atmospheric plasma; oral biofilm; periodontitis
    DOI:  https://doi.org/10.3389/fcimb.2026.1915920
  4. Annu Rev Virol. 2026 Sep;13(1): 135-153
    Phages Targeting Flagella: Adsorption and Infection Mechanisms of Flagellotropic Phages.
    Jackson A Wood, Nathaniel C Esteves, Birgit E Scharf.
      Bacteriophages (phages) are viruses that exclusively infect bacteria. They adsorb to their hosts through binding to cell receptors including flagella, pili, or lipopolysaccharide (LPS). Adsorption is a two-step process, with reversible adhesion to cell surface receptors followed by irreversible binding. Many phages and all known flagellotropic phages belong to the class Caudoviricetes, which encompasses tailed phages with double-stranded DNA genomes. Most flagellotropic phages adsorb reversibly to the flagella of their host and traverse the flagellum to reach the cell surface. Next, secondary receptors, such as LPS or pili portals, may then mediate irreversible binding and DNA ejection. Because flagellar motility is an important virulence factor in many bacterial pathogens, flagellotropic phages could be useful to treat or prevent bacterial infections or contaminations. For a broader application, host-range expansion techniques can be applied. The Appelmans protocol, which involves passaging multiple, closely related phages through successive cultures of susceptible and nonsusceptible bacteria, relies on recombination and spontaneous mutations to generate chimeric phages. These newly evolved phages with a broadened host range are promising candidates for phage therapy. A better understanding of flagellotropic phage infection mechanisms and their host-range expansion might lead to the successful use of flagellotropic phages as therapeutics.
    Keywords:  antibiotic resistance; evolutionary trade-off; host phage interaction; phage therapy; phage training; receptor binding protein
    DOI:  https://doi.org/10.1146/annurev-virology-100424-123335
  5. Arch Microbiol. 2026 Sep 21. pii: 657. [Epub ahead of print]208(12):
    Bacteriophage-bacteria coevolution: from molecular arms races to ecological and applied perspectives.
    Junjie Shang, Linghui Li, Chengqian Dong, Yunlin Wei.
      Bacteriophages are the most abundant biological entities, driving bacterial evolution through long-term coevolution. Bacteria have evolved diverse defense strategies against phage, including receptor modification, restriction-modification systems, CRISPR-Cas, abortive infection systems, and newly discovered systems such as BREX, DISARM, CBASS, Thoeris, and Zorya. In response, phages deploy countermeasures such as receptor-binding diversification, anti-CRISPR proteins, DNA modification, and inhibitors targeting host immunity. These interactions generate distinct evolutionary dynamics-arms race and fluctuating selection-shaping microbial population structure and ecological stability. Phage-host coevolution promotes microbial diversity, horizontal gene transfer, and regulates community composition across ecosystems. Understanding these processes is critical for applications like phage therapy, microbiome engineering, and biotechnology. This review summarizes molecular mechanisms of bacterial defense and phage counter-defense, discusses coevolutionary models, highlights ecological and applied implications, and outlines future research directions.
    Keywords:  Antiviral defense systems; Bacteria; Bacteriophage; Coevolution; Phage counter-defense
    DOI:  https://doi.org/10.1007/s00203-026-05221-w
  6. Nat Med. 2026 Sep 21.
    A consensus-based guideline for personalized bacteriophage therapy.
    guideline group ‘Personalized Bacteriophage Therapy’ of the Association of the Scientific Medical Societies in Germany
      Bacteriophages (phages) - viruses that selectively infect bacteria - are a promising option for personalized therapy of difficult-to-treat bacterial infections. Clinical implementation in many countries worldwide, however, faces multiple hurdles, including a lack of consensus on general principles for phage therapy, infrastructural requirements, procedures for quality-assured phage selection and preparation, clinical administration, monitoring and documentation. Existing guidance provides limited practical direction across the entire translational pathway and lacks inspection-ready specifications to support both pharmacies and clinical sites. These gaps impede safe and transparent clinical use and effective regulatory oversight. Likewise, there are no established processes to identify research questions that will be key to advancing clinical phage research in the future. To address these needs, this consensus-based guideline was developed within the methodological framework of the Association of the Scientific Medical Societies in Germany under the leadership of the German Society for Infectious Diseases. It was created through a collaborative effort involving 20 professional societies, patient advocacy groups and regulatory authorities and 18 international experts. The guideline provides over 60 recommendations on core principles, infrastructure, preparation and quality control, administration and future research. Recommendations are supported by international societies, organizations and stakeholders. By providing clear and practice-oriented recommendations, this consensus statement paves the way for the safe and standardized use of personalized phage therapy.
    DOI:  https://doi.org/10.1038/s41591-026-04654-6
  7. Int J Mol Sci. 2026 Sep 12. pii: 8138. [Epub ahead of print]27(18):
    The Wound-Heart Axis: Can Chronic Wounds Contribute to Cardiac Dysfunction?
    Preeti K Chaudhary, Howard H Chen, Lakshmi Pulakat.
      Traditionally, chronic wounds including diabetic foot ulcers (DFUs), pressure ulcers (PUs), venous leg ulcers (VLUs), arterial ulcers, inflammatory and autoimmune-associated ulcers, infected chronic wounds, and non-healing post-surgical wounds are treated as localized diseases of skin and soft tissue damage. However, these lesions are increasingly acknowledged as chronic inflammatory states with consequences extending beyond the wound bed and often arising in the setting of systemic dysfunction. Across wound types, shared features include persistent inflammation, oxidative stress, endothelial dysfunction, immune imbalance, protease dysregulation, infection or biofilm burden, metabolic disturbance, and impaired regenerative signaling. These abnormalities may promote systemic cytokine release, vascular dysfunction, neurohumoral activation, oxidative injury, and maladaptive remodeling. Cardiac dysfunction is already known to impair wound healing. In contrast, whether chronic non-healing wounds are associated with or may contribute to cardiac damage resulting in heart failure remains insufficiently defined. Emerging epidemiologic and mechanistic evidence suggests that chronic non-healing wounds may amplify cardiovascular stress, particularly in vulnerable patients with diabetes, obesity, frailty, kidney disease, or pre-existing vascular disease. This narrative review explores the conceptual hypothesis that chronic non-healing wounds may contribute to systemic cardiovascular stress and cardiac dysfunction. It integrates clinical and mechanistic opportunities, outlines potential pathways, including extracellular vesicle (EV) signaling, and highlights key knowledge gaps and therapeutic implications in the wound-heart axis.
    Keywords:  cardiac dysfunction; cardiovascular risk; chronic wounds; inflammation; wound–heart axis
    DOI:  https://doi.org/10.3390/ijms27188138
  8. Vet Res Commun. 2026 Sep 21. pii: 584. [Epub ahead of print]50(6):
    From laboratory to clinical application: a narrative review of bacteriophage therapy for antimicrobial-resistant infections in veterinary medicine.
    Natália Chomová, Gabriel Žoldák, Dagmar Mudroňová.
      Antimicrobial resistance poses one of the most critical challenges to global health, particularly within veterinary medicine, where antibiotic misuse contributes significantly to multidrug-resistant infections. Bacteriophages have re-emerged as promising biocontrol agents that can target resistant pathogens while preserving host microbiota and environmental balance. However, despite growing experimental evidence, therapeutic implementation remains constrained by heterogeneous methodologies, limited clinical validation, and fragmented regulatory frameworks. This narrative review critically appraises advances in veterinary phage therapy and suggests that standardized, optimized bacteriophages may match the efficacy and biosafety of antibiotics, potentially enhancing their effectiveness in combination therapies. Latest studies report substantial pathogen reduction and, in a smaller number of cases, improved clinical outcomes in livestock (Escherichia coli, Staphylococcus aureus, Salmonella enterica, Clostridium perfringens), as well as in aquaculture (Aeromonas hydrophila, Edwardsiella tarda) and apiculture (Paenibacillus larvae) models. Emerging strategies, including phage cocktails, microencapsulation, and phage-antibiotic synergy, enhance therapeutic stability but require standardized evaluation. To fully realize their potential, bacteriophage therapies must be developed within harmonized frameworks that integrate genomic surveillance, pharmacodynamic modeling, and quality-controlled production. Phage therapy should thus be viewed not as an established alternative but as a dynamic, hypothesis-driven approach capable of reshaping antimicrobial stewardship within the "One Health" paradigm.
    Keywords:  Antimicrobial resistance; Bacteriophages; One health; Phage therapy; Therapeutic standardization; Veterinary medicine
    DOI:  https://doi.org/10.1007/s11259-026-11518-4
  9. Antibiotics (Basel). 2026 Sep 06. pii: 870. [Epub ahead of print]15(9):
    Rational Design of a Phage Cocktail for Effective Control of Multidrug-Resistant Uropathogenic Escherichia coli from Hospitalized Patients.
    Patiphan Khunti, Panupon Mongkolkarvin, Songphon Buddhasiri, Joe Pogliano, Poochit Nonejuie, Parameth Thiennimitr, Vorrapon Chaikeeratisak.
       BACKGROUND: The emergence of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) poses a significant public health challenge, and alternative treatments are urgently needed.
    METHODS: Here, we identified clinical MDR-UPEC strains AT82 and AT84 collected from hospitalized patients that display extensive antimicrobial resistance at both genetic and phenotypic levels. Due to their high resistance profile, we systematically customized a phage cocktail from our coliphage library using hierarchical clustering based on host specificity and candidate selection through bacterial suppression profiles.
    RESULTS: This pipeline yielded four lytic coliphages, designated Phi25-4, Phi25-6, Phi50-4, and Killian. Their genomes are relatively large ranging from 112-169 kbp and cluster into two distinct lineages comprising two closely related groups: Phi25-4/Phi50-4 and Phi25-6/Killian. Although each phage exhibited potent antibacterial activity, none alone sustained bacterial suppression during prolonged treatment. To overcome this limitation, we systematically compared the antibacterial activity of all possible phage combinations.
    CONCLUSIONS: The four-phage cocktail outperformed all two- or three-phage formulations, sustaining significant growth inhibition of AT82 and AT84 for up to 16 h and reducing area under the curve by more than 80% relative to controls. Cocktail potency was dose-dependent, with lower phage doses yielding the least viable cells at 48 h. Additionally, this cocktail exerted prophylactic action, significantly reducing UPEC invasion by several orders of magnitude, while the phage cocktail alone induced minimal proinflammatory cytokine responses in human bladder epithelium. Together, these findings provide an effective phage cocktail and a complementary framework for cocktail design against urinary tract infections caused by MDR bacteria.
    Keywords:  MDR; MDR-UPEC; UPEC; bacteriophage; phage; phage therapy
    DOI:  https://doi.org/10.3390/antibiotics15090870
  10. Int J Mol Sci. 2026 Sep 11. pii: 8108. [Epub ahead of print]27(18):
    Urinary Tract Infections: Molecular Determinants of Uropathogenicity and Their Translation into Contemporary Clinical Practice.
    Raul-Lucian Ene, Roxana Popescu, Aurica Elisabeta Cobec, Melinda Kali, Ileana-Adriana Ene, Daliborca Cristina Vlad, Peter Seropian, Ionut Marcel Cobec.
      Urinary tract infections (UTIs) represent a major global health burden, traditionally defined as microbial invasion of a sterile urinary tract, but now increasingly understood as a state of microbial dysbiosis involving disruption of the urinary microbiome. This review aims to synthesize current knowledge on the molecular mechanisms, etiological agents, clinical classification, and emerging therapeutic strategies in UTIs. The analysis integrates recent advances in microbiome research, molecular pathogenesis, and clinical guidelines. Uropathogenic Escherichia coli (UPEC) remains the predominant pathogen, utilizing virulence factors such as adhesins and intracellular bacterial community formation to establish persistent infection, while other organisms including Klebsiella pneumoniae, Proteus mirabilis, and Enterococcus faecalis contribute to disease complexity. The emergence of multidrug-resistant organisms, particularly among ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), poses significant therapeutic challenges through mechanisms such as β-lactamase production, efflux pumps, and biofilm formation. Clinically, evolving classification systems emphasize infection localization rather than host factors, improving diagnostic and therapeutic precision. Diagnostic strategies rely on clinical assessment, urinalysis, and urine culture, while treatment increasingly incorporates antimicrobial stewardship principles. Emerging approaches, including immunoprophylaxis, bacteriophage therapy, and microbiome-targeted interventions, demonstrate promising results. In conclusion, UTIs are complex, multifactorial diseases requiring integrated molecular, clinical, and therapeutic approaches, with future advancements likely driven by precision medicine and artificial intelligence.
    Keywords:  ESKAPE pathogens; Uropathogenic Escherichia coli (UPEC); antimicrobial resistance; bacteriophage therapy; complicated UTI; immunoprophylaxis; intracellular bacterial communities; urinary microbiome; urinary tract infections
    DOI:  https://doi.org/10.3390/ijms27188108
  11. Biomed Pharmacother. 2026 Sep 22. pii: S0753-3322(26)00930-3. [Epub ahead of print]204 119894
    Bridging the gap between experimental evidence and clinical applications of antipseudomonal phage therapy against Pseudomonas aeruginosa.
    Ahmed Elfadadny, Wedad M Nageeb, Rokaia F Ragab, Hazim O Khalifa.
      Pseudomonas aeruginosa is one of the World Health Organization's (WHO) priority pathogens requiring urgent intervention because of its remarkable ability to develop antimicrobial resistance. The rapid emergence and global dissemination of multidrug-resistant P. aeruginosa have made the treatment of these infections increasingly challenging, posing a major threat to public health worldwide. Consequently, there is an urgent need for alternative therapeutic strategies. Bacteriophage (phage) therapy has re-emerged as a promising antimicrobial approach for combating drug-resistant bacterial infections. Numerous in vitro, in vivo, and clinical studies have demonstrated the therapeutic potential of antipseudomonal phages, either as monotherapy or in combination with antibiotics. In this review, we comprehensively summarize the current evidence on antipseudomonal phage therapy, including laboratory investigations, animal studies, and personalized clinical applications. We further discuss the pharmacological and clinical considerations, major challenges limiting clinical translation, and the current knowledge gaps that hinder widespread implementation. Finally, we highlight key research priorities that should be addressed to facilitate the safe, effective, and evidence-based integration of bacteriophage therapy into routine clinical practice.
    Keywords:  Clinical application; P. aeruginosa; Phage therapy; Research gaps; Resistance
    DOI:  https://doi.org/10.1016/j.biopha.2026.119894
  12. Front Microbiol. 2026 ;17 1873220
    Precision phage therapy in the AI/ML era: a systematic review of discovery-to-clinical translation evidence.
    Najwa Menwer Alharbi.
      In precision phage therapy, artificial intelligence and machine learning (AI/ML) is being applied for phage detection, genomes/proteome annotation, host prediction, resistance profiling and therapeutic optimization. Yet the landscape remains fragmented owing to a lack of systematic synthesis of its translational maturity, methodological robustness and pipeline coverage. We performed a systematic review of AI/ML tools relevant to precision phage therapy. Web of Science, PubMed, MEDLINE, Scopus and IEEE Xplore were used to identify records. Of 6,969 identified records, 2,214 duplicates were removed, leaving 4,755 unique records for title/abstract screening; 510 full-text articles were assessed for eligibility, and 128 studies were included in the final synthesis. Studies were classified across a nine-module precision phage therapy pipeline by architectural family, validation maturity, accessibility, translational readiness (AI_PTRL), and methodological quality using an adapted PROBAST framework. The 128 included studies were published between 2012 and 2025, with a median publication year of 2023 and peak activity during 2022-2025. The large majority were methodological/tool development studies (115/128, 89.8%) and these predominantly described in silico validation (101/128, 78.9%). The pipeline coverage was uneven, with the highest concentration in the host range and interaction determinants (M4, 43/128, 33.6%) and genome/protein annotation and functional inference (M3, 33/128, 25.8%). Safety screening, therapeutic design, and infrastructure modules were comparatively underrepresented. From an architectural standpoint, hybrid/integrated systems (HIS) (39/128, 30.5%) and classical machine learning (CML) (38/128, 29.7%) were the most common approaches with substantial diversification after 2022. The overall translational readiness was modest (median AI_PTRL: 6, IQR 4-6). Methodological assessment demonstrated high evaluation risk of bias (104/128, 81.2%) and substantial development concern (88/128, 68.8%), especially in Domain 4 (analysis). AI/ML for precision phage therapy is a rapidly growing and diversifying field, particularly in host-phage interaction prediction, however efforts are still limited for downstream precise phage therapy tasks. Experimental validation and real-world deployment remain limited with methodological limitations due to analytical design and evaluative approaches. Future work should prioritize rigorous validation frameworks, higher-quality and more complete representative datasets, stronger safety screening, therapeutic optimization, and clinically actionable decision support.
    Keywords:  antimicrobial resistance; artificial intelligence; clinical translation; foundation models; genome annotation; graph neural networks; host–phage interaction; machine learning
    DOI:  https://doi.org/10.3389/fmicb.2026.1873220
  13. Biology (Basel). 2026 Sep 10. pii: 1596. [Epub ahead of print]15(18):
    Mapping Bacteriophage-Based Antimicrobial Research in Southeast Asia: A Bibliometric Analysis of Scientific Productivity, Knowledge Structure, and Emerging Research Pathways.
    Christian Joseph N Ong, Johnalie N Cabalbag, Jowi Tsidkenu Pili Cruz, Teodora T Valderama, Celia R Roslin, Carina M Magtibay, Janice Kaylyn K Lonogan, Amelda C Libres, Joel G Matamis, Jose Edwardo R Mamaat, Ferdinand A Mortel, Grace D Bacalzo, Kevin Smith P Cabuhat, Carlos S de Leon, Jose Jurel M Nuevo, Joel R Aguilan, Jamil Allen G Fortaleza.
      Southeast Asia faces a substantial burden of antimicrobial resistance (AMR), creating increasing interest in bacteriophage-based antimicrobial strategies. However, the regional development, contributors, collaboration patterns, and evolving research priorities of this field remain insufficiently characterized. This study conducted a bibliometric analysis of Scopus-indexed publications on bacteriophage-based antimicrobial research affiliated with Southeast Asian countries from 1981 to 2025. Bibliometrix/Biblioshiny and VOSviewer were used to evaluate scientific production, citation patterns, leading contributors, collaboration networks, and conceptual and thematic development. A total of 862 publications were analyzed, with scientific output accelerating markedly after 2019 and reaching its highest level in 2025. Thailand emerged as the dominant regional contributor, with Vongkamjan (n = 21) and Surachat (n = 20) as the two most prolific authors. Mahidol University (n = 182), Prince of Songkla University (n = 142), and Universiti Putra Malaysia (n = 139) were the leading institutions, demonstrating a concentration of research capacity in Thailand and Malaysia. Scientific Reports was the most productive journal (30 publications), whereas Frontiers in Microbiology recorded the highest citation count among the leading sources (963 citations). Collaboration mapping revealed increasingly interconnected regional and international research networks. Thematic analyses demonstrated a transition from foundational and pathogen-specific investigations toward AMR, bacteriophage therapy, biofilm control, aquaculture, genomic and comparative genomic analysis, wastewater and public-health applications, and One Health-oriented research. Emerging topics included endolysins, quorum sensing, CRISPR-associated approaches, metagenomics, and genome-informed phage characterization. These findings demonstrate the rapid expansion and thematic diversification of bacteriophage-based antimicrobial research in Southeast Asia while highlighting persistent geographic concentration and the need for stronger regional infrastructure, collaboration, and translational capacity.
    Keywords:  Southeast Asia; antimicrobial resistance; bacteriophage; bibliometric analysis; phage therapy; research trends
    DOI:  https://doi.org/10.3390/biology15181596
  14. PLoS Biol. 2026 Sep 22. 24(9): e3004009
    Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance.
    Heng Xue, Xinfeng Li, Guibo Rao, Fen Hu, Mingyue Zhong, Paulina Miernikiewicz, Rui Qiu, Sheng Cao, Krystyna Dąbrowska, Hang Yang.
      Phage therapy represents a promising strategy to tackle the growing threat of antimicrobial resistance. Increasing evidence has demonstrated that phage-specific antibodies may compromise the efficacy of phage therapy. Nevertheless, little is known about how phage protein specificity of antibodies modulates phage therapeutic outcomes. Herein, we utilized AbP20, a podovirus against Acinetobacter baumannii, to explore the effects of antibodies elicited by each structural protein on phage therapy efficacy in a mouse infection model. Intraperitoneal administration of AbP20 once a day for 7 consecutive days induced robust phage-specific antibody responses that impaired phage therapy. Genome-guided antigen screening identified that antibodies elicited by the nozzle and fiber proteins of AbP20, rather than those targeting the portal, capsid, or adaptor proteins, are the dominant drivers of phage therapy failure. Specifically, fiber-specific and nozzle-specific antibodies block bacterial adsorption and genomic injection of AbP20, respectively. Meanwhile, both antibody subsets efficiently induce large phage aggregates and potentiate macrophage phagocytosis via an Fc receptor-independent pathway. An evolved AbP20 variant with improved neutralization escape capacity exhibited comparable antibody-accelerated phagocytosis and host immune clearance, yet partially rescued therapeutic failure caused by neutralizing antibodies. Collectively, this study elucidates that nozzle- and fiber-elicited neutralizing antibodies impair phage therapy via dual synergistic mechanisms, which offers novel insights into the multifaceted modulation of phage-specific antibodies against phage therapeutic efficacy.
    DOI:  https://doi.org/10.1371/journal.pbio.3004009
  15. Medicina (Kaunas). 2026 Aug 28. pii: 1651. [Epub ahead of print]62(9):
    Artificial Intelligence and Bioengineering Approaches for Antimicrobial Resistance Prediction.
    Oana Frandeș, Leonard Azamfirei, Oana Elena Branea, Sergiu Ioan Frandeș, Alexandra Elena Lazăr.
      Background and Objectives: Antimicrobial resistance (AMR) is a major challenge, particularly in intensive care units, where broad-spectrum therapy is often initiated before microbiological confirmation. Artificial intelligence (AI) may improve AMR prediction, but its clinical value depends on integration with bioengineering-enabled digital microbiology. This narrative review examines how AI, bioengineering platforms and digital microbiology can support AMR prediction, clinical decision support and antimicrobial stewardship across the sample-to-decision pipeline. Materials and Methods: A targeted narrative review was conducted using PubMed/MEDLINE and Google Scholar. Publications from 2020 onward were prioritized, while earlier seminal studies, methodological frameworks and regulatory documents were included when relevant. Evidence was synthesized across AI-based resistance prediction, antimicrobial stewardship, digital microbiology and bioengineering technologies. Results: AI and machine-learning approaches showed promising performance in patient-level resistance prediction, pathogen-level susceptibility prediction and antimicrobial stewardship. For example, model discrimination reached an AUROC of 0.936 for carbapenem-resistant Klebsiella pneumoniae prediction, while model-guided empirical therapy in Enterobacterales bloodstream infections could have increased active beta-lactam therapy from 70% to 79%. However, most evidence remains retrospective and single-centre, with limited external or prospective validation. Conclusions: AI has considerable potential to support AMR prediction and antimicrobial stewardship, but current evidence primarily demonstrates technical feasibility rather than established clinical effectiveness. Broader implementation will require rigorous validation, integration into clinical workflows, continuous monitoring and demonstration of clinical benefit.
    Keywords:  MALDI-TOF MS; antimicrobial resistance; antimicrobial stewardship; artificial intelligence; bioengineering; clinical decision support; intensive care unit; machine learning; whole-genome sequencing
    DOI:  https://doi.org/10.3390/medicina62091651
  16. Front Microbiol. 2026 ;17 1921205
    Genomic and functional characterization of six novel phages targeting multidrug-resistant Escherichia coli: promising candidates for clinical phage therapy.
    Lingling Xiong, Xiaolian Shen, Yingying Xiang, Jingting Sun, Ting Wang, Qian Zhou, Kehui Xiong, Wenxue Wang, Jiawei Geng, Xiuling Ji.
      Antimicrobial resistance in multidrug-resistant Escherichia coli has severely compromised the efficacy of conventional antibiotics, particularly in hospital-acquired infections. Bacteriophage therapy offers a targeted approach, yet the rapid emergence of phage-resistant mutants during monotherapy limits its durability. However, phage cocktail therapy can overcome this issue. In this study, we isolated and characterized six novel lytic bacteriophages from hospital wastewater that specifically infect MDR E. coli clinical isolates. All six phages exhibited strictly lytic lifestyles, and genomic analysis confirmed the absence of lysogeny, virulence, or antibiotic-resistance genes. They are promising candidates for phage cocktail therapy. Stability assays demonstrated that the phages maintained activity under various temperature and pH conditions. Adsorption kinetics showed rapid binding to host cells, and one-step growth curves indicated efficient lytic replication with short latent periods and high burst sizes. Moreover, the phages consistently reached high titers (1010-1012 PFUs/mL) and demonstrated potent activity against preformed biofilms of MDR E. coli strains. Phylogenetic analyses placed these phages within distinct clusters, supporting their genetic diversity. Together, these findings expand current understanding of the biology and diversity of E. coli-targeting phages and provide a robust foundation for the rational design of phage cocktails aimed at overcoming persistent MDR E. coli infections.
    Keywords:  Escherichia coli; antimicrobial resistance; bacteriophage; biofilm; phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2026.1921205
  17. Microorganisms. 2026 Sep 15. pii: 2055. [Epub ahead of print]14(9):
    The Human Vaginal Virome: Composition, Microbiome Interactions, and Implications for Bacterial Vaginosis, HPV Persistence, and Preterm Birth.
    José Eleutério Junior, Paulo César Giraldo, Renata Mírian Nunes Eleutério, Cristiana Rodrigues Teófilo.
      Important gaps remain in our understanding of the vaginal virome. Its composition, interactions with the bacterial microbiome and host immune system, and implications for vaginal homeostasis, human papillomavirus (HPV) persistence, and obstetric outcomes remain incompletely defined. The vaginal virome is a dynamic component of the female genital ecosystem. It includes viruses that infect human cells, bacteriophages, and endogenous viral elements. Observational studies have associated altered viral composition or diversity with vaginal dysbiosis, persistent HPV detection, and adverse pregnancy outcomes, including preterm birth. These relationships remain correlative, and causality has not been established. Bacteriophage-based therapies and recombinant endolysins may selectively target bacterial biofilms associated with bacterial vaginosis. However, most applications remain preclinical or in early clinical development. Better characterization of the interactions among viruses, bacteria, epithelial cells, and mucosal immunity may support future diagnostic biomarkers and precision therapeutic strategies in women's health.
    Keywords:  bacteriophages; human papillomavirus; phage therapy; preterm birth; vaginal dysbiosis; vaginal microbiome; vaginal virome
    DOI:  https://doi.org/10.3390/microorganisms14092055
  18. Prog Mol Biol Transl Sci. 2026 ;pii: S1877-1173(26)00176-6. [Epub ahead of print]224 195-223
    Microbial allies in malignancy: Role of Porphyromonas gingivalis and Candida biofilms in oral squamous cell carcinoma.
    Saikat Mazumder, Debasmita Bhattacharya, Sudhriti Maity, Trisha Dutta, Sayan Chatterjee.
      Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and it is becoming clear that it is a multifactorial disease condition that is affected by microbial dysbiosis. Porphyromonas gingivalis and Candida spp. are keystone periodontal pathogens that have become key disease initiators and progressors in the formation of polymicrobial biofilms in periodontal disease. The biofilms are hyper-virulent, resistant, and cooperate metabolically, leading to chronic inflammation and epithelial remodelling. P. gingivalis, in a mechanistic way, regulates host signaling pathways such as NF- kB, PI3K/Akt, and MAPK to induce anti-apoptotic and proliferative responses, and Candida biofilms trigger carcinogenesis by producing acetaldehyde, disrupting the epithelial barrier, and activating oncogenic pathways. This interaction between bacteria and fungal elements is further synergistic and leads to immune evasion, redox dysbalance, and chronic inflammation, which form a tumor-promoting microenvironment. The implication of emerging evidence also includes the effects of microbial metabolites, quorum sensing, and biofilm architecture in determining the OSCC niche. Notably, such polymicrobial interactions offer new therapeutic avenues, such as anti- biofilm therapy, modulation of microbiomes, and targeted molecular therapy. This chapter thoroughly addresses the mechanistic contributions of P. gingivalis and Candida biofilms to OSCC pathogenesis with a specific focus on their synergistic contribution and potential translational implications in diagnosis, prevention, and treatment.
    Keywords:  Candida spp.; Microbiome-mediated carcinogenesis; Oral squamous cell carcinoma; Polymicrobial biofilms; Porphyromonas gingivalis
    DOI:  https://doi.org/10.1016/bs.pmbts.2026.07.009
  19. Expert Rev Clin Pharmacol. 2026 Sep 25.
    Non-antibiotic therapeutic approaches for antimicrobial resistance: current evidence and future directions.
    Bharath Kumar Ganesan, Archana Mishra, Debasish Hota, Rituparna Maiti.
       INTRODUCTION: Antimicrobial resistance (AMR) is a global health challenge that reduces the effectiveness of existing antibiotics, leading to increased morbidity, mortality and healthcare costs worldwide. The lack of the development of novel classes of antibiotics has led to an increased interest in non-antibiotic therapeutic approaches that focus on bacterial virulence, host-pathogen interactions, microbial ecology, and resistance mechanisms.
    AREAS COVERED: This review summarizes the current evidence on non-antibiotic therapeutics including bacteriophages, antimicrobial peptides, anti-virulence agents, monoclonal antibodies, microbiome-based therapies, CRISPR-Cas systems, nanoparticles, photodynamic therapy, repurposed non-antibiotic drugs and combination strategies. We performed a literature search on PubMed, Embase, Scopus, Web of Science, and Google Scholar until May 2026. Though several approaches have demonstrated promising biological activity and favorable safety profiles, clinical evidence remains limited and heterogeneous.
    EXPERT OPINION: Non-antibiotic therapeutics are vital adjunctive, salvage and precision approaches to the challenge of AMR. However, most strategies are still at an early translational stage with a paucity of high-quality randomized clinical evidence. Barriers include delivery, manufacturing complexity, regulatory uncertainty, cost, and lack of long-term safety data. Further progress will depend on standardization of production, better delivery platforms, well-designed multicentric clinical trials, and incorporation into antimicrobial stewardship and precision medicine frameworks.
    Keywords:  Antimicrobial resistance; CRISPR-Cas systems; Non-antibiotic therapeutics; antimicrobial peptides; bacteriophage therapy
    DOI:  https://doi.org/10.1080/17512433.2026.2739560
  20. Mol Biol Rep. 2026 Sep 23. pii: 1610. [Epub ahead of print]53(1):
    Inflammasome-derived biomarkers in wound healing: linking tissue repair, chronic inflammation, fibrosis, and precision therapeutics.
    Rahul A Sachdeo, Chitra Khanwelkar, Amol Shete, Sarika J Patil, Nilam B Pawar.
      Wound healing is a highly organised biological event that involves hemostasis, inflammation, proliferation, and tissue remodelling processes. Dysregulated wound healing leads to the development of chronic wounds, characterised by persistent inflammation, impaired tissue regeneration, and extensive fibrosis. Recently, inflammasomes, which act as key regulators of innate immunity, have attracted increasing attention due to their important roles in wound healing. Indeed, inflammasome complexes, including NLRP3, AIM2, NLRC4, NLRP1, and Pyrin, activate inflammatory caspases, particularly caspase-1, which cleaves pro-IL-1β and pro-IL-18 into their mature, biologically active forms and promotes gasdermin D-dependent pyroptosis. Although transient inflammasome activation contributes to protective early inflammatory responses, including pathogen clearance and tissue repair, sustained or dysregulated activation promotes inflammatory caspase activation and pyroptosis, resulting in persistent inflammation, tissue injury, and aberrant extracellular matrix remodelling that can ultimately contribute to fibrosis and chronic wound development. This review focuses on state-of-the-art studies on the roles of inflammasome-derived biomarkers in wound healing. We highlight inflammasome-associated molecules as potential biomarkers of wound inflammation and tissue injury, while distinguishing their roles as mechanistic mediators from their potential as therapeutic targets. These include sensors, adaptors, inflammatory caspases, pyroptosis-related mediators, cytokines, and oxidative stress-associated factors. Our review highlights transcriptomic, proteomic, and metabolomic approaches for identifying candidate molecular biomarkers, while single-cell RNA sequencing and spatial transcriptomics provide cell-specific and spatial information that can improve biomarker validation and clinical stratification of wound states. Additionally, we discuss shared inflammasome-mediated mechanisms across diabetic foot ulcers, pressure ulcers, venous leg ulcers, burn wounds, and fibrotic scars, while highlighting condition-specific triggers, including metabolic dysfunction in diabetes, ischemia-reperfusion in pressure ulcers, venous hypertension, thermal injury, and dysregulated tissue remodelling in fibrosis.
    Keywords:  Biomarkers; Chronic wounds; Fibrosis; Inflammasomes; Precision medicine; Wound healing
    DOI:  https://doi.org/10.1007/s11033-026-12783-x
  21. Antibiotics (Basel). 2026 Sep 12. pii: 899. [Epub ahead of print]15(9):
    Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical Pipeline.
    Melanie Kempf Hansen, Lars Østergaard.
       BACKGROUND/OBJECTIVES: Antimicrobial resistance (AMR) is an urgent global threat, with bacteria developing resistance against most antibiotics currently in clinical use. Non-traditional antibacterials-including bacteriophages, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), live biotherapeutic products (LBPs) and anti-virulence small molecules-act through mechanisms distinct from traditional antibiotics and may exhibit mechanism-dependent differences in the propensity for resistance development. Despite growing interest, the landscape of non-traditional candidates in active clinical development against WHO priority pathogens has not been recently systematically mapped. This review aimed to characterize the current non-traditional antibacterial clinical pipeline targeting pathogens on the WHO Bacterial Priority Pathogens List (BPPL) 2024.
    METHODS: Candidates were identified from the WHO antibacterial clinical pipeline report (October 2025) and verified through the Global AMR R&D Hub, ClinicalTrials.gov, and targeted searches of peer-reviewed publications, conference abstracts, and company communications. Candidates were included if they showed documented clinical activity since January 2023.
    RESULTS: Twenty-seven candidates met the inclusion criteria, of which 20 remain in active clinical development and seven have been discontinued or paused or have unverified status. The pipeline is dominated by bacteriophages and markedly skewed toward carbapenem-resistant Pseudomonas aeruginosa (CRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with few or no candidates targeting carbapenem-resistant Acinetobacter baumannii (CRAB), Shigella or Salmonella.
    CONCLUSIONS: Non-traditional antibacterials represent a promising but underfunded and unevenly distributed pipeline-with public and philanthropic investment in antibacterial R&D totaling just $2.51 billion across 2017-2023, a seven-year total, against an estimated $251-276 billion in global pharmaceutical R&D spending in a single recent year. Realizing their potential will require substantially greater investment and more deliberate prioritization toward the WHO priority pathogens currently underserved by the non-traditional pipeline.
    Keywords:  WHO priority pathogens; antibiotics; antimicrobial peptides; antimicrobial resistance; bacteriophage therapy; live biotherapeutic products; monoclonal antibodies; non-traditional antibacterials
    DOI:  https://doi.org/10.3390/antibiotics15090899
  22. Access Microbiol. 2026 ;pii: 001146.v3. [Epub ahead of print]8(9):
    Lytic bacteriophages targeting carbapenem-resistant Klebsiella pneumoniae isolated in a resource-limited Zambian laboratory.
    Frank Chilombolwa Nyondo, Bwalya Daka Lalusha, Marriot Chikopa, Sody Munsaka.
      Klebsiella pneumoniae is a major cause of healthcare-associated and community-acquired infections, increasingly complicated by multidrug resistance (MDR) and carbapenem-resistant K. pneumoniae (CRKp). Phage-based approaches are attractive in such settings but rely on infrastructure and expertise, which are not widely available in low-resource laboratories. Here, we describe the isolation and preliminary characterization of two lytic K. pneumoniae phages, Zm_01 and Zm_02, from hospital sewer sludge in Lusaka, Zambia, using only routine microbiology equipment and simple adaptations of standard protocols. Clinical K. pneumoniae isolates, including MDR and carbapenem-resistant (meropenem-resistant) strains, were used for enrichment, double-agar overlay plaque assays, host-range screening and determination of efficiency of plating (EOP). Zm_01, isolated on a non-MDR but hypermucoviscous host, produced small, clear plaques and exhibited efficient plating on several MDR isolates, with EOP values higher on some MDR strains than on its original host. Zm_02, isolated on an MDR strain, formed large, clear plaques with halos, consistent with capsule-degrading activity. All work was performed without access to specialized equipment, such as a spectrophotometer, a shaker incubator or standard imaging equipment. These findings demonstrate that discovery and basic phenotypic characterization of therapeutically relevant K. pneumoniae phages are feasible in low-resource settings and provide a practical workflow that can underpin future functional and genomic studies, as well as the development of locally tailored phage-based interventions against MDR and CRKp infections.
    Keywords:  Klebsiella pneumoniae; antimicrobial resistance; bacteriophages; carbapenem-resistant Klebsiella pneumoniae; multidrug resistance; phage therapy
    DOI:  https://doi.org/10.1099/acmi.0.001146.v3
  23. Pharmaceuticals (Basel). 2026 Sep 16. pii: 1465. [Epub ahead of print]19(9):
    Phage Genomics and Bioinformatics in Therapeutic Development: Evidence Limits, Validation Gates, and Translational Decision-Making.
    Mia Yang Ang, Li Chen, Lanni Song, Leonard Lipovich, Siew Woh Choo.
      Background/Objectives: Antimicrobial resistance has renewed interest in live therapeutic phages, including engineered candidates and defined phage cocktails, as antibacterial strategies. However, clinical translation requires evidence extending beyond phage isolation and computational prediction. This review examines how phage genomics and bioinformatics can support phage-based antibacterial development while remaining aligned with pharmaceutical requirements for safety, quality, pharmacology, and clinical validation. Methods: This narrative review synthesizes the literature on the generation, interpretation, and experimental validation of genomic and bioinformatic evidence for live therapeutic phages. Representative approaches for viral identification, genome-quality assessment, annotation, comparative genomics, lytic-temperate lifestyle classification, host prediction, receptor analysis, antiphage-defence profiling, and artificial-intelligence-assisted prioritization were evaluated according to their outputs, principal failure modes, validation requirements, and supported development decisions. Results: Current tools address distinct analytical tasks. Examples include VIBRANT and geNomad for viral identification, CheckV and PhageTerm for genome-quality and termini assessment, Pharokka, PHANOTATE, and PHROGs for gene prediction and annotation, PhageAI, BACPHLIP, and PhaTYP for lytic-temperate lifestyle prediction, iPHoP and CRISPR spacer matching for host prioritization, and PADLOC and DefenseFinder for bacterial defence profiling. Their outputs differ in taxonomic resolution, reference coverage, training-data dependence, and biological interpretation. The review maps these outputs to proportionate validation requirements while integrating formulation and PK/PD context, sequence-to-product traceability, intellectual-property documentation, minimum-information reporting, and resistance-responsive redesign. Conclusions: This review presents a practical sequence-to-product framework for interpreting contemporary phage-bioinformatics methods. By separating computational discovery from isolate-level activity, product quality, pharmacological evidence, and clinical monitoring, it clarifies the decisions supported at each stage and the additional evidence required before candidate progression, product use, or redesign.
    Keywords:  antibacterial biopharmaceuticals; bacteriophage therapy; bioinformatics; genome-informed risk assessment; phage cocktails; phage genomics; phage-antibiotic combinations; phage-host prediction; product quality; regulatory science
    DOI:  https://doi.org/10.3390/ph19091465
  24. Pathogens. 2026 Sep 09. pii: 963. [Epub ahead of print]15(9):
    Biofilm Dynamics and Antimicrobial Resistance in Rabbit Odontogenic Infections: A One Health Perspective.
    Ramona Ioana Stîngă, George Cosmin Nadăş.
      Rabbit odontogenic abscesses are among the most challenging chronic infections encountered in exotic animal medicine because of their polymicrobial etiology, biofilm-associated persistence, and poor response to conventional antimicrobial therapy. Biofilm formation plays a central role in disease pathogenesis by promoting bacterial adhesion, extracellular polymeric substance (EPS) production, quorum sensing (bacterial cell-to-cell communication), metabolic heterogeneity, and the persister-cell formation (transiently antibiotic-tolerant bacterial subpopulations), collectively reducing antimicrobial susceptibility and contributing to treatment failure and recurrence. In addition to biofilm-mediated tolerance, antimicrobial resistance (AMR) further complicates disease management through mechanisms including horizontal gene transfer, efflux pump activation, enzymatic antibiotic degradation, reduced membrane permeability, and target modification. This review summarizes current knowledge on the microbiology, biofilm dynamics, and resistance mechanisms associated with rabbit odontogenic infections while examining recent advances in molecular diagnostics, including culture-independent sequencing technologies, metagenomics, and advanced imaging approaches. Current and emerging anti-biofilm strategies, such as local antimicrobial delivery systems, enzymatic biofilm disruption, quorum-sensing inhibitors, bacteriophage therapy, antimicrobial peptides, photodynamic therapy, and nanotechnology-based approaches, are critically discussed in the context of their potential application in rabbits. Comparative evidence from human endodontic infections and other veterinary biofilm-associated diseases highlights the translational relevance of rabbit odontogenic abscesses as a naturally occurring model for chronic polymicrobial infections. Finally, key research gaps are identified, emphasizing the need for standardized experimental models, integrated multi-omics analyses, combining genomic, transcriptomic, proteomic, and metabolomic data, longitudinal clinical investigations, and evidence-based antimicrobial stewardship. By integrating microbiology, biofilm biology, antimicrobial resistance, and One Health concepts, this review provides a comprehensive framework to support future research and improve the diagnosis, treatment, and prevention of rabbit odontogenic infections.
    Keywords:  One Health; antimicrobial resistance; biofilms; dental disease; oral microbiome; rabbit odontogenic abscesses
    DOI:  https://doi.org/10.3390/pathogens15090963
  25. Prog Mol Biol Transl Sci. 2026 ;pii: S1877-1173(26)00188-2. [Epub ahead of print]224 169-193
    Biofilms and beyond: The impact of Porphyromonas gingivalis on oral squamous cell carcinoma.
    Souradip Basu.
      Oral squamous cell carcinoma (OSCC) appears as a very common type of head and neck cancer across the world in the recent past. The widespread use of contemporary diagnostic and prognostic methods, a low rate of survival (approximately five-year), a relatively higher chances towards recurrence, and a wide range of malignancy along with metastases are still caused by delayed diagnosis and treatment resistance. There is growing evidence that oral microbiome bacteria, including the Gram-negative anaerobic Porphyromonas gingivalis, may be important in the development of OSCC by causing periodontitis. In fact, the activity of a dysbiotic microbiota has been linked to the epithelial-to-mesenchymal transition (EMT) and dysregulated immune response. Conversely, organisms that are typically thought of as oral commensals, including streptococci from the mitis group, are frequently negatively correlated and have anticancer qualities in vivo. This chapter summarizes the role of P. gingivalis in OSCC initiation, progression, invasion, and metastatic dissemination, highlighting its contribution to microbial dysbiosis, immune modulation, epithelial-mesenchymal transition, and tumor microenvironment remodelling. Several reports have showed a positive correlation exist between the bacteria present in the periodontal part along with oral carcinoma. This would in turn pave the way for future researchers to target P. gingivalis as a potential therapeutic cornerstone to combat the life-threatening diseases.
    Keywords:  Microbial dysbiosis; Oral biofilms; Oral squamous cell carcinoma (OSCC); Porphyromonas gingivalis; Therapeutic potential
    DOI:  https://doi.org/10.1016/bs.pmbts.2026.08.001
  26. Microorganisms. 2026 Sep 10. pii: 2013. [Epub ahead of print]14(9):
    Innovative Applications of Artificial Intelligence in Bacteriophage Research: A New Chapter in Future Medicine.
    Dapeng Yang, Xin Yuan, Yubao Li.
      As the crisis of antibiotic resistance escalates, phage therapy has regained attention as an alternative strategy. Artificial intelligence (AI) technologies offer new avenues to overcome the bottlenecks inherent in traditional bacteriophage research. This review summarizes the multi-dimensional innovative applications of machine learning, deep learning, and large biological models in phage studies. In the fields of phage recognition and genomics, support vector machines (SVMs), convolutional neural networks (CNNs), and pre-trained protein language models can all achieve recognition accuracy rates of over 90%. Furthermore, tools such as DeepHost and VirSorter2 can efficiently identify phage sequences, annotate functional genes, and predict hosts at the species or strain levels. For clinical translation, AI integrates patient characteristics, bacterial phenotypes, and phage profiles to customize cocktail regimens for individualized phage therapy. Graph neural network-based models like DeepPBI-KG integrate multi-omics knowledge graphs to precisely predict phage-host interactions (PHIs), whereas agent-based simulation and defense protein predictors forecast phage resistance evolution. Additionally, generative AI can support the de novo design of functional phage genomes and mine massive unannotated virome dark matter. Nevertheless, this cross-disciplinary field faces significant constraints, including uneven and biased sequencing datasets, insufficient model interpretability, and dual-use biosafety ethical risks accompanied by unclear algorithm accountability and incomplete global supervision systems. Future research should optimize standardized multimodal databases, develop explainable AI algorithms, and establish cross-disciplinary ethical governance frameworks to facilitate closed-loop verification between computational prediction and wet-lab experiments. In conclusion, the deep integration of AI and phage biology provides revolutionary strategies to tackle multidrug-resistant infections and advances the clinical transformation of phage precision medicine.
    Keywords:  artificial intelligence; deep learning models; machine learning; phage; phage-host interaction
    DOI:  https://doi.org/10.3390/microorganisms14092013
  27. Basic Clin Pharmacol Toxicol. 2026 Oct;139(4): e70307
    Vitamins and Chronic Wounds: How Altered Pharmacokinetics and Comorbidities Contribute to Vitamin Deficiencies.
    Michiel G J Balvers, Teuntje L de Smit, Anne I Slotegraaf, Remy H H Bemelmans, Joé L P Kolkert, Tim J Schuijt, Renger F Witkamp.
      Wound healing is complex and requires adequate amounts of macro- and micronutrients. When wound healing is delayed, a wound is considered chronic. Increasing evidence shows that vitamin deficiencies are prevalent in patients with chronic wounds, yet intervention studies with vitamin supplementation yielded inconsistent effects. These inconsistencies may be explained by suboptimal study designs and vitamin doses. To substantiate optimal dosing, it is important to understand how vitamin pharmacokinetics and requirements are altered in patients with chronic wounds. However, a comprehensive overview of factors that influence vitamin kinetics during wound repair is lacking. This review aims to address this. A multitude of interfering factors may co-exist in individuals with chronic wounds, including medication, malabsorption, inflammation, as well as overweight, obesity and renal insufficiency. Several of these factors are linked to diabetes and advancing age as overarching factors. Limited evidence suggests that vitamin requirements may be higher in individuals with diabetes. More work is needed to understand vitamin pharmacokinetics and vitamin requirements in patients with chronic wounds. Data on the effects of the treatment of combinations of deficiencies, and for B-vitamins, are entirely lacking. Healthcare professionals should be aware of the prevalence and risk factors for vitamin deficiencies in populations with chronic wounds, and monitoring of blood concentrations may be warranted. Provisional recommendations are made on how to treat and prevent vitamin deficiencies.
    DOI:  https://doi.org/10.1111/bcpt.70307
  28. Expert Rev Anti Infect Ther. 2026 Sep 26. 1-12
    Novel options for the management of C. difficile: a look into the future.
    Guido Granata, Nicola Petrosillo, Fabrizio Taglietti.
       INTRODUCTION: Clostridioides difficile infection (CDI) remains one of the leading causes of healthcare-associated diarrhea; additionally, evidence suggests a growing incidence of community-acquired CDI worldwide. CDI is characterized by substantial morbidity, mortality, and risk of recurrence. CDI underdiagnosis and recurrent CDI represent a major unmet clinical need, highlighting the need for innovative diagnostic, preventive and therapeutic strategies.
    AREAS COVERED: This perspective article summarizes emerging approaches that may shape the future management of CDI, including novel microbiome-sparing antimicrobials, fecal microbiota transplantation (FMT), live biotherapeutic products, C. difficile vaccines, bacteriophage-derived therapies, CRISPR-Cas technology and artificial intelligence (AI) applications.
    EXPERT OPINION: Future CDI management is expected to evolve toward precision medicine focused on microbiome preservation, prevention of recurrence, and individualized patient care. Novel antimicrobials such as ibezapolstat and CRS3123, phage-derived approaches, and CRISPR-guided antimicrobials may provide highly targeted alternatives to conventional treatments. Microbiota-based therapies will evolve to assume an increasingly central role in reducing microbiota disruption. Simultaneously, advances in diagnostics, vaccine development, and AI-driven predictive tools may improve risk stratification, therapeutic selection, and infection prevention and control. All these innovative strategies have the potential to redefine CDI prevention and treatment, although robust clinical validation and long-term safety data remain essential.
    Keywords:  Artificial intelligence; Bacteriophage therapy; CRISPR-Cas; Clostridioides difficile; fecal microbiota transplantation; live biotherapeutic products; microbiome-preserving and -restoration strategies; vaccines
    DOI:  https://doi.org/10.1080/14787210.2026.2739273
  29. Antibiotics (Basel). 2026 Sep 08. pii: 879. [Epub ahead of print]15(9):
    Phage-Antibiotic-Peptide Synergy Overcomes Biofilm-Mediated Multidrug Resistance in Serratia marcescens.
    Aryaan P Duggal, Adit B Alreja, Isha Vashee, Hayley Nordstrom, Erin Harrelson, Nakia Fallen, Kari-Ann Takano, Ryan A Blaustein, Derrick E Fouts, Norberto Gonzalez-Juarbe.
      Background/Objectives: Serratia marcescens is an opportunistic pathogen that causes severe hospital-acquired infections, notable for its biofilm formation abilities and development of extensive antibiotic resistance. Here, we aim to evaluate the efficacy of bacteriophages, antibiotics, and antimicrobial peptides (BAP), alone and in combination, against fourteen multidrug-resistant (MDR) S. marcescens isolates sourced from hospitals and other environmental settings.
    METHODS: S. marcescens was grown planktonically or in surface-associated biofilms, and biofilm biomass was measured via changes in absorbance and colony-forming units or live/death staining.
    RESULTS: Combining bacteriophage with a low-dose cocktail of penicillin-streptomycin, kanamycin, and ciprofloxacin enhanced antimicrobial activity compared with antibiotics alone. Across the isolate panel, responses to BAP treatment varied according to determined antibiotic resistance profiles. The highly resistant AR-0517 isolate was selected for detailed mature biofilm analysis, where the BAP treatment reduced biofilm biomass by 97.8% and recoverable bacteria by 99.99%. Microscopy and viability assays further confirmed extensive biofilm disruption and bacterial killing.
    CONCLUSIONS: These findings demonstrate that simultaneous targeting of multiple bacterial pathways can enhance antimicrobial activity against MDR S. marcescens in vitro and support further evaluation of BAP as a potential strategy for biofilm-associated infections.
    Keywords:  Serratia marcescens; antibiotic; antimicrobial peptides; biofilms; phage
    DOI:  https://doi.org/10.3390/antibiotics15090879
  30. Infect Dis Rep. 2026 Sep 07. pii: 98. [Epub ahead of print]18(5):
    The Role of Infrared Thermography in the Diagnosis and Monitoring of Diabetic Foot Infection: A Systematic Review.
    Carmen Cantarero-Lozano, Aroa Tardáguila-García, Esther García-Morales, Yolanda García-Álvarez, David Navarro-Pérez, José Luis Lázaro-Martínez.
       BACKGROUND: Diabetic foot infection (DFI) is one of the most frequent diabetes-related complications requiring hospitalisation and is a major contributor to lower-extremity amputation. Infrared thermography has emerged as a non-invasive diagnostic tool capable of detecting temperature changes associated with inflammatory and infectious processes. This systematic review aimed to evaluate the role of thermography in the diagnosis and monitoring of diabetic foot infection.
    METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Risk of bias and methodological quality were assessed using design-specific validated tools, including QUADAS-2 for diagnostic and detection studies and Joanna Briggs Institute critical appraisal checklists for cohort and case-series studies. Original studies evaluating the use of thermography in patients with diabetic foot infection were included. Two authors independently performed study selection, data extraction, and methodological assessment.
    RESULTS: Six studies met the inclusion criteria, comprising a total of 552 participants with type 1 or type 2 diabetes mellitus. Four observational studies and two pilot studies were included. Increased local skin temperature was consistently associated with acute diabetic foot complications and infection. Several studies identified a temperature difference of approximately 2.2 °C between contralateral foot regions as a clinically relevant threshold for detecting diabetic foot complications. However, no significant relationship was found between plantar thermal asymmetry and the severity or progression of infected diabetic foot ulcers. All included studies presented a level of evidence of 4 and a grade of recommendation of C.
    CONCLUSIONS: Infrared thermography appears to be a promising adjunctive tool for the early detection of diabetic foot infection. However, current evidence does not support its routine use for monitoring infection severity, treatment response, or prognosis, and further prospective studies are required before these applications can be recommended.
    Keywords:  diabetic foot; diabetic foot infection; diabetic foot ulcer; infrared thermography; thermography
    DOI:  https://doi.org/10.3390/idr18050098
  31. Probiotics Antimicrob Proteins. 2026 Sep 14.
    Animal-Derived Antimicrobial Peptides: Emerging Therapeutic Strategies against Multidrug-Resistant Pathogens.
    Mallu Mallikarjuna, Narasimha Golla.
      The global escalation of antimicrobial resistance (AMR) has outpaced the conventional antibiotic discovery pipeline, with bacterial AMR associated with an estimated 4.71 million deaths in 2021 and forecast to contribute to rising mortality through 2050. The World Health Organization's 2024 Bacterial Priority Pathogens List continues to identify carbapenem-resistant Gram-negative organisms and rifampicin-resistant Mycobacterium tuberculosis as the most urgent targets for new therapeutics. Antimicrobial peptides (AMPs), ancient and evolutionarily conserved effectors of innate immunity, are one of several candidate classes under active investigation. The animal kingdom, spanning mammals, amphibians, fish, insects, arachnids, and venomous taxa, is a structurally and functionally diverse reservoir of these molecules, and this diversity has already attracted several recent, more narrowly focused reviews covering venom-derived, marine-derived, and computationally designed AMPs. The present narrative review instead undertakes a cross-taxon comparative synthesis, explicitly distinguishing native animal peptides, proteolytic fragments of animal proteins, and synthetic analogues derived from an animal scaffold from the bacterial and fungal peptide antibiotics sometimes discussed alongside them. We survey the principal structural families and their taxonomic sources, compare their membrane-disruptive and intracellular mechanisms, and critically assess their anti-biofilm activity by distinguishing biofilm prevention from eradication of established biofilms. We examine the molecular determinants of bacterial resistance to AMPs with reference to the primary mechanistic literature, and we compile a verified, trial-identifier-referenced account of clinical development that separates candidates with completed Phase III evaluation from those with only preclinical or unverified clinical support. Every animal-derived AMP evaluated in a controlled human trial to date has either failed to demonstrate superiority over an existing comparator or remains restricted to topical or localised use; none has achieved new systemic regulatory approval. Against this evidence base, we argue that the realistic near-term contribution of animal-derived AMPs lies in combination therapy with existing antibiotics and in topical or localised indications with direct clinical evidence, while their use as stand-alone systemic agents remains a preclinical and early-clinical prospect rather than an established therapeutic reality.
    Keywords:  Antimicrobial peptides; Cathelicidins; Defensins; ESKAPE pathogens; Host defence peptides; Innate immunity; Multidrug resistance; Venom-derived peptides; antibiotic alternatives; peptide therapeutics
    DOI:  https://doi.org/10.1007/s12602-026-11225-1
  32. Int J Nanomedicine. 2026 ;21 624310
    Antimicrobial Strategies for Chronic Cutaneous Ulcers: From Preclinical Nanotechnology to Clinical Practice.
    Myriam González, Gabriela E Galarza-Arévalo, Cristina Garzón-Romero, Maria P Romero.
      Chronic cutaneous ulcers represent a growing global public health challenge, affecting an estimated 1-2% of the population in high-income countries and imposing a substantial socioeconomic burden through prolonged hospitalizations, repeated outpatient visits, increased risk of amputation, and significant impairment of patients' quality of life. Standard wound care centered on debridement, moisture-balancing dressings, and systemic antibiotics fails to resolve a large proportion of cases, particularly those complicated by polymicrobial biofilm infection and antimicrobial resistance, underscoring an urgent need for more effective therapeutic strategies. Despite the growing body of work on individual therapeutic modalities, no prior review has jointly evaluated clinically validated adjunct therapies and preclinical nanoplatform evidence for chronic cutaneous ulcers within a single, biofilm-ecology-centered framework, the gap this review addresses. This review critically evaluates current clinical and preclinical advances in the treatment of chronic cutaneous ulcers, with a focus on novel therapeutic modalities and emerging nanotechnology-based approaches. Clinically, the available evidence indicates that low-intensity ultrasound, electrical microcurrent therapy, photodynamic therapy, regenerative biomaterials, oxygen-based interventions, and advanced topical therapies may improve wound contraction, reduce microbial burden, relieve pain, and enhance tissue repair when used as adjuncts to standard care. At the preclinical level, metallic, polymeric, inorganic, and hybrid nanoplatforms can simultaneously target resistant bacteria and biofilms, stimulate angiogenesis, regulate inflammatory signaling, and support extracellular matrix remodeling. Recent advances in ulcer therapy are moving the field beyond passive wound coverage toward mechanism-driven treatments that actively modulate the chronic wound microenvironment. Despite this progress, current clinical evidence remains inconsistent and is often limited by small patient cohorts and non-standardized protocols. This highlights the pressing need for rigorous translational research to incorporate multifunctional bioactive platforms into well-supported, ulcer-specific therapeutic strategies.
    Keywords:  angiogenesis; antimicrobial resistance; biofilm-associated infection; chronic wounds; diabetic foot ulcers; nanomedicine; precision wound care; wound microbiome
    DOI:  https://doi.org/10.2147/IJN.S624310
  33. Thorax. 2026 Sep 21. pii: thorax-2026-225527. [Epub ahead of print]
    International epidemiology of antimicrobial resistance in people living with chronic lung infection.
    Ollie Pitts, Chiara Premuda, ZhiLing Yuan, Mattia Nigro, Till Othmer, Nikolas Johl, Arafa Aboelhassan, Safaa Eid, Sarah Hashem, Noha Khalil, Michael Behnke, Oto Melter, Pavel Drevinek, Rishi Dhillon, Irfan Shafiq, Nilüfer Acet-Öztürk, Ozge Aydin Guclu, Daniela Girelli, Jamie Duckers, Wang Chun Kwok, Stefano Aliberti, Andrea Gramegna, Stephanie Thee, Frederick Frost, Anand Shah.
       BACKGROUND: Antimicrobial resistance (AMR) is a global threat for people with chronic lung infection; however, international AMR epidemiology in bronchiectasis and cystic fibrosis (CF) is poorly characterised. In this study, we retrospectively analyse international longitudinal AMR epidemiology in bronchiectasis and CF.
    METHODS: Microbiology data were analysed from 110 323 respiratory samples in 19 143 individuals with bronchiectasis or CF across 11 cities, eight countries, three continents between 2011 and 2024. Longitudinal AMR prevalence, multidrug-resistant (MDR) and extensively drug-resistant (XDR) prevalence and multiple antibiotic resistance (MAR) index were analysed by disease and country. Pilot analysis of concurrent/disjoint resistance in antimicrobial pairs and triplets in regional datasets was performed to inform combination or cyclical antimicrobial choice.
    FINDINGS: Geographic AMR differences were noted across pathogens in bronchiectasis and CF with increased Pseudomonas aeruginosa resistance in central/southern Europe and increased Klebsiella pneumoniae resistance in Hong Kong. MDR burden was high in emergent pathogens Escherichia coli (CF: MDR 32.6%; XDR 12.4%; bronchiectasis: MDR 39.2%; XDR 4.9%) and K. pneumoniae (CF: MDR 22.7%; XDR 15.6%; bronchiectasis: MDR 13.4%; XDR 1.5%). A longitudinal rise in P. aeruginosa AMR was seen in bronchiectasis across four centres for antipseudomonal aminoglycosides (p<0.001; OR/year 1.44; 95% CI 1.24 to 1.67), fluoroquinolones (p=0.002; OR/year 1.13; 95% CI 1.05 to 1.23), cephalosporins (p=0.005; OR/year 1.17; 95% CI 1.05 to 1.30), penicillins with beta-lactamase inhibitor (p=0.02; OR/year 1.18; 95% CI 1.03 to 1.35) and carbapenems (p=0.048; OR/year 1.11; 95% CI 1.00 to 1.23). Rising longitudinal K. pneumoniae AMR was seen for cephalosporins (p=0.01; OR/year 1.32; 95% CI 1.06 to 1.65) and carbapenems (p=0.04; OR/year 1.64; 95% CI 1.03 to 2.62). A significant increase in AMR, as measured by the MAR index, was observed in individuals with residual culture-positive CF receiving triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (p<0.001). Strong concurrent resistance was noted in bronchiectasis across regions with geographic variation in disjoint antimicrobial pair resistance.
    CONCLUSION: We show a significant increasing international AMR burden in bronchiectasis and CF, with geographic variation and persistence post-CFTR modulator therapy.
    Keywords:  Bacterial Infection; Bronchiectasis; Cystic Fibrosis
    DOI:  https://doi.org/10.1136/thorax-2026-225527
  34. Antibiotics (Basel). 2026 Sep 17. pii: 919. [Epub ahead of print]15(9):
    Modeling Phage-Antibiotic Synergy, Innate Immunity, and Phage Resistance in Multidrug-Resistant Acinetobacter baumannii.
    Alma Karen Orozco-Ochoa, José Benigno Valdez-Torres, Jean Pierre González-Gómez, Nohelia Castro-Del Campo, Cristóbal Chaidez-Quiroz.
      Background/Objectives: Antimicrobial resistance has been recognized as a major global health threat, with multidrug-resistant Acinetobacter baumannii identified as one of the most critical pathogens. To address the limitations of conventional antibiotics, phage therapy has been proposed as a complementary or alternative intervention. In this study, experimental data were integrated into a deterministic differential-equation-based model to capture phage-bacteria-antibiotic-host immune system interactions. Methods: The model extended a previous phage-host immune system synergy framework by incorporating phage-antibiotic synergy and a time-dependent reduction in phage adsorption as a phenomenological representation of population-level reduction in phage susceptibility. This formulation does not explicitly model the molecular mechanisms or evolutionary emergence of resistance. In vitro observations of phage-induced resensitization to ceftazidime informed model parameterization, while remaining parameters were estimated from experimental observations or literature values. Simulations evaluated bacterial dynamics under phage-only, antibiotic-only, and immunity-only conditions, as well as combined therapeutic scenarios. Results: Model predictions indicated the greatest bacterial reduction when phages, antibiotics, and host innate immunity acted together. Phage-antibiotic synergy further enhanced predicted bacterial clearance, particularly for ceftazidime-resistant populations, while a population-level reduction in phage susceptibility was predicted approximately 4 h post-infection, consistent with experimental observations. Combined scenarios involving continuous antibiotic infusion, phage plus host immunity, or low-dose antibiotic regimens predicted accelerated bacterial declines when synergistic interactions were active. Conclusions: This framework integrates experimental observations with mathematical modeling to explore therapeutic interactions and temporal changes in phage susceptibility, while assessing parameter sensitivity and guiding future experimental and preclinical studies.
    Keywords:  antimicrobial resistance; computational modeling; host–pathogen interactions; mathematical model; phage susceptibility; phage–antibiotic synergy
    DOI:  https://doi.org/10.3390/antibiotics15090919
  35. Viruses. 2026 Aug 28. pii: 942. [Epub ahead of print]18(9):
    Isolation and Genomic Characterisation of Five Novel Lytic Bacteriophages Infecting the Emerging Pathogen Klebsiella grimontii.
    Anna Tokmakova, Anna Lukianova, Mikhail Shneider, Ilia Putilov, Maria Filatova, Anna Burtseva, Konstantin M Boyko, Yuliya Mikhailova, Andrey Shelenkov, Elizaveta Popova, Konstantin Miroshnikov.
      Klebsiella grimontii is an emerging pathogen associated with multidrug resistance. Although a single recent study reported phages against K. grimontii, their taxonomic diversity and structural characterisation remained limited. Here, we describe the isolation and characterisation of five novel lytic bacteriophages that specifically target K. grimontii strain K15g, originally isolated from a rotting iris rhizome. Phages Silvester, Lyra, Lyris, Mirion, and Helios were isolated from wastewater samples collected in the Moscow region and represent three distinct morphotypes: podovirus (Silvester), siphovirus (Lyra, Lyris, Mirion), and myovirus (Helios). Whole-genome sequencing revealed that Silvester belongs to the genus Przondovirus (family Autographiviridae); Lyra, Lyris, and Mirion are members of the genus Sugarlandvirus (family Demerecviridae); and Helios falls within the genus Slopekvirus (family Straboviridae). All five phages lack genes associated with lysogeny, virulence factors, or antibiotic resistance, indicating their suitability for therapeutic applications. Structural modelling of the receptor-binding proteins revealed diverse architectures of adsorption apparatuses, including a two-depolymerase complex in Silvester, T5-like tail fibres in the Sugarlandvirus phages, and a set of long and short fibres with a structured cell-puncturing device in Helios. This study presents five novel phages active against Klebsiella grimontii and provides a basis for further evaluation of their potential in phage therapy.
    Keywords:  Klebsiella grimontii; Przondovirus; Slopekvirus; Sugarlandvirus; bacteriophage; phage therapy; structural modelling
    DOI:  https://doi.org/10.3390/v18090942
  36. Nat Microbiol. 2026 Sep 25.
    Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ.
    Dorentina Humolli, Damien Piel, Jessica Ransome, Kathrin Bausch, Sarah Tschudin-Sutter, Monica Ortelli, Christoph Dehio, Jan-Willem Veening, Alexander Harms.
      The arms race of bacteriophages and their bacterial hosts has inspired major breakthroughs in biotechnology and shaped phages as fierce predators with great clinical potential to fight multidrug-resistant bacterial pathogens. However, the large amount of genes of unknown function in phage genomes remains a major obstacle for the molecular understanding of phage-host interactions. Here we present HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing), a transposon-insertion sequencing method for phages that systematically links viral genes to selectable phenotypes. Using model phage T4, we show that HIDEN-SEQ readily reproduces the gene essentiality map established over decades of research. Our method is easily portable across diverse non-model phages and reveals conditionally essential genes in multiple bacterial hosts and growth conditions, including previously unknown antidefence factors that we matched to specific antiviral defences. We anticipate that HIDEN-SEQ will be leveraged to reveal functions of viral genes with direct relevance for microbial ecology, biotechnology and phage therapy.
    DOI:  https://doi.org/10.1038/s41564-026-02455-8
  37. Microbiol Spectr. 2026 Sep 24. e0128526
    Deciphering the modular structure of phage depolymerase: a dual-action strategy for biofilm degradation and targeted Pseudomonas aeruginosa binding.
    Yu-Chuan Tsai, Ling-Chun Lin.
      Pseudomonas aeruginosa is a critical ESKAPE pathogen that can form strong biofilms, which protect it from antibiotics and the host's immune system. Enzymes from bacteriophages, called depolymerases, are often found in tail fiber proteins and provide a useful way to break down these biofilms. In this work, we studied ORF55, a tail fiber protein from Pseudomonas phage phiPA1-3 that contains an SGNH hydrolase domain. Using AlphaFold2 for structural modeling and modular dissection, we identified the specific functions of its N-terminal and C-terminal parts. We found that the full protein (SGNH55_Full) broke down easily. However, a shorter version that kept the SGNH hydrolase domain (SGNH55Δtail_619) was much more stable and better at degrading biofilms. This truncated enzyme worked well against biofilms from clinical isolates, including those resistant to phages. This shows it has broad potential for treatment that does not depend on the virus itself infecting the bacteria. At the same time, we identified the N-terminal domain (TFP55) as the part responsible for binding to the bacterial receptor. We used TFP55 to develop a fast latex agglutination test to detect P. aeruginosa. This test was very specific and sensitive, with a limit of detection of 10 CFU, and it stayed stable for 6 months. Our results show that breaking down phage tail fibers into modules is a powerful strategy. It provides a clear path for creating both effective anti-biofilm agents and stable tools for diagnosis.IMPORTANCEBiofilm-forming Pseudomonas aeruginosa poses severe clinical challenges, and full-length phage depolymerases, while promising, are often unstable. This study overcomes this limitation through the structure-guided modular dissection of the phage tail fiber protein SGNH55. By decoupling its catalytic and host-binding domains, we generated two highly stable tools: a potent enzyme to eradicate multidrug-resistant biofilms and a sensitive diagnostic probe for rapid pathogen detection. This dual-utility approach provides an innovative therapeutic-diagnostic strategy and establishes a universal framework for engineering complex phage proteins.
    Keywords:  Pseudomonas aeruginosa; SGNH hydrolase; bacteriophage; biofilm; depolymerase; tail fiber protein
    DOI:  https://doi.org/10.1128/spectrum.01285-26
  38. Gels. 2026 Sep 06. pii: 817. [Epub ahead of print]12(9):
    Albumin Hydrogels Loading Bacteriophage PA57 as a Promising Platform for Pseudomonas aeruginosa Infection Management.
    Inna Zharkova, Tatiana Ushakova, Yulia Tupikova, Oksana Gulyaeva, Vera Morozova, Yulia Kozlova, Nina Tikunova, Elena Dmitrienko.
      The global proliferation of multidrug-resistant Pseudomonas aeruginosa stimulates the search for alternatives to conventional therapy. This study developed human serum albumin (HSA)-based hydrogels for the delivery of bacteriophage PA57. Matrices were fabricated via combined thermal- and ethanol-induced gelation. The release kinetic was dependent on protein concentration: 20% (w/v) HSA provided sustained release over 48 h, whereas 10-15% (w/v) HSA exhibited burst release effects. Combined systems effectively suppressed P. aeruginosa growth in vitro during the early and middle stages of incubation, maintaining low culture optical density for up to 28 h. Although late-stage bacterial regrowth was observed, the final bacterial load remained significantly lower than in the control. Furthermore, cytocompatibility assays with HaCaT keratinocytes and MRC-5 fibroblasts demonstrated high cell viability, confirming the safety of the hydrogel matrix for wound healing applications. These results demonstrate the promise of HSA-based hydrogels as a platform for localized phage therapy of infected wounds.
    Keywords:  Pseudomonas aeruginosa; bacteriophage PA57; drug delivery; human serum albumin; hydrogel; infected wounds
    DOI:  https://doi.org/10.3390/gels12090817
  39. J Spec Oper Med. 2026 Sep 25. pii: J.Spec.Oper.Med.2026.M1XC-G0IV. [Epub ahead of print]
    Non-Battle Injury in Military Operations Novel Treatment for Soft Tissue Injury and Infection with Logistics Implications.
    J Rick Hammesfahr.
       BACKGROUND: Non-battle injuries (NBIs) represent a substantial proportion of morbidity during military deployments, often exceeding combat-related injuries in frequency. NBIs, including superficial wounds, burns, blisters, and soft tissue infections, remain a significant source of lost duty time and operational disruption in deployed military populations. In austere environments with limited medical support, even minor injuries often progress to cellulitis or abscess, which require substantial logistical resources including irrigation fluids, medical dressings, and antibiotics, impairing operational readiness.
    METHODS: This review synthesizes epidemiologic data, clinical outcomes, and logistical considerations from surveillance reports, peer-reviewed publications and Department of War guidelines. Rates of wound progression, hospitalization, and duty loss were analyzed alongside logistics modeling based on U.S. Army Clinical Practice Guidelines (CPGs).
    RESULTS: Evidence indicates that 15%-20% of untreated superficial wounds develop infection, 3%-7% progress to cellulitis or abscess, and 1%-2% require hospitalization. Blister-related cellulitis contributes significantly to lost duty time, with up to 120-150 duty days lost per 100 infections. Standard CPG-based wound care requires multiple liters of irrigation fluid, frequent dressing changes, and systemic antibiotics. Novel products such as Field Shield™ Wound Dressing and KeriCleanz™ Antiseptic that are optimized for ease of use and multiple applications per product show potential to reduce infection rates and resupply burdens, decreasing fluid and dressing requirements while conserving antibiotics.
    CONCLUSION: Early recognition and aggressive management of superficial wounds and preventative measures for managing minor injuries such as blisters and skin infections are essential for both clinical recovery and sustaining combat effectiveness.
    Keywords:  cellulitis; medical logistics; military medicine; non-battle injuries; operational readiness; soft tissue infection; wound care
    DOI:  https://doi.org/10.55460/J.Spec.Oper.Med.2026.M1XC-G0IV
  40. Pathogens. 2026 Aug 26. pii: 898. [Epub ahead of print]15(9):
    Neglected ESKAPE Pathogens in Companion Animals: Diagnostic Bias, Zoonotic Blind Spots, and Phytotherapeutic Opportunities.
    Codruța Emilia Conțiu, Cosmina Maria Bouari, Nicodim Iosif Fiț, George Cosmin Nadăş, Sorin Răpuntean.
      The emergence of antimicrobial resistance among ESKAPE pathogens represents a major One Health challenge, yet several clinically relevant members of this group remain underrecognized in companion animals because of diagnostic limitations and research bias. This review critically evaluates current evidence on neglected ESKAPE pathogens in dogs and cats, with particular emphasis on diagnostic blind spots, antimicrobial resistance, zoonotic implications, and the potential of phytotherapeutic strategies. A structured literature search of PubMed, Scopus, and Web of Science, complemented by reports from international health organizations, was conducted to identify studies addressing pathogen occurrence, resistance mechanisms, transmission pathways, and plant-derived antimicrobial compounds. The available evidence indicates that organisms such as the Enterobacter cloacae complex, Stenotrophomonas maltophilia, Enterococcus faecium, and Acinetobacter baumannii remain substantially underinvestigated despite their clinical relevance and multidrug-resistant phenotypes. Advanced diagnostic approaches, including MALDI-TOF MS and whole-genome sequencing, together with integrated One Health surveillance, may improve their detection and epidemiological characterization. Current phytotherapeutic research demonstrates promising antibacterial, antibiofilm, and antibiotic-potentiating activities of plant-derived compounds but remains largely focused on well-characterized pathogens. Targeted investigation of neglected ESKAPE pathogens using chemically characterized plant extracts and clinically relevant veterinary isolates may support the development of complementary antimicrobial strategies and strengthen antimicrobial stewardship within the One Health framework.
    Keywords:  ESKAPE pathogens; GC-MS; One Health; antimicrobial resistance; biofilm; companion animals; diagnostic bias; phytotherapy; plant-derived antimicrobials; zoonotic transmission
    DOI:  https://doi.org/10.3390/pathogens15090898
  41. Antibiotics (Basel). 2026 Sep 12. pii: 900. [Epub ahead of print]15(9):
    Receptor Structure Shapes Host Range but Incompletely Predicts High Activity in Klebsiella pneumoniae Phage Cocktails.
    Roman B Gorodnichev, Anastasiia O Krivulia, Maryam O Sidorskaia, Maria A Kornienko, Narina K Abdraimova, Maja V Malakhova, Marina V Zaychikova, Dmitry A Bespiatykh, Egor A Shitikov.
       BACKGROUND: Rational design of phage cocktails typically relies on the lytic spectrum. However, susceptibility criteria vary widely among studies, ranging from qualitative lysis in spot tests to quantitative endpoints based on serial-dilution titration or efficiency of plating.
    METHODS: We investigated this discrepancy using four commercial phage cocktails and two capsule-specific monophages against a clinically representative collection of 448 Klebsiella pneumoniae isolates comprising 56 capsule types, collected in 2018-2025 from 12 medical centers. Using a modified Gratia titration assay, we defined host range (HR) as specific lysis at any dilution and putative therapeutic applicability (PTA) as lysis at dilutions corresponding to ≥106 plaque-forming units per mL.
    RESULTS: We identified a systematic discrepancy between these two measures of cocktail efficacy. HR coverage reached 64%, whereas PTA was significantly lower, with a median HR-PTA difference of 36%. This discrepancy persisted for capsule-specific monophages tested against KL2 isolates (n = 69), indicating that neither nominal capsule matching nor low component titres fully explained the loss of activity. This pattern provides indirect functional evidence that post-adsorption barriers contribute to the HR-PTA discrepancy, although adsorption and intracellular antiphage mechanisms were not assessed directly. Capsule type was the principal and most robust predictor of efficacy, whereas spatiotemporal factors, including year and medical centre, had only a weak effect on PTA.
    CONCLUSIONS: Capsule matching can therefore help estimate population-level coverage but does not fully predict high-titre activity. Phage selection should incorporate serial-dilution testing rather than rely on spot-test lysis alone. Cocktail design should account for both receptor coverage and functional activity against representative isolates within individual capsule types.
    Keywords:  Klebsiella pneumoniae; bacteriophage therapy; host range; phage cocktails; phage susceptibility testing; post-adsorption resistance; rational cocktail design
    DOI:  https://doi.org/10.3390/antibiotics15090900
  42. Int Wound J. 2026 Sep;23(9): e71045
    Diabetic Foot Ulcer-Associated Versus Other Lower-Extremity Necrotising Soft-Tissue Infections: A Retrospective Cohort Study.
    Haowu Tang, Wenchao Guo, Jun He, Xinzhu Song, Kai Wang, Xin Zhang, Zhou Jin, Xiaorui Jiang.
      To compare clinical characteristics, microbiology, treatment burden and outcomes between lower-extremity necrotising soft tissue infections associated with diabetic foot ulcers (DFU) and lower-extremity necrotising soft tissue infections not associated with DFU. We retrospectively reviewed 86 surgically treated patients at a single tertiary hospital from 2015 to 2025. Twenty patients had diabetic foot ulcer-associated infections and 66 had infections from other causes. Baseline characteristics, laboratory findings, microbiology, resource utilisation, wound healing, amputation and mortality were compared between the cohorts. The diabetic foot ulcer-associated group had a longer diabetes duration, higher glycated haemoglobin and a greater prevalence of hypertension, coronary heart disease and chronic kidney disease. Microbiological profiles showed overlapping distributions of major pathogens. The proportion of patients who were alive with a healed wound at 90 days was lower in the DFU-associated group (35.0% vs. 80.3%), and overall amputation was more frequent (55.0% vs. 15.2%), primarily driven by minor amputation (40.0% vs. 1.5%). Major amputation (15.0% vs. 13.6%) and mortality (10.0% vs. 4.5%) did not differ statistically, although estimates were imprecise. Lower-extremity necrotising soft tissue infections associated with DFU were associated with greater comorbidity, resource utilisation, minor amputation and a lower proportion of patients alive with a healed wound at 90 days. This retrospective study cannot determine whether minor amputation improves survival or prevents major amputation.
    Keywords:  amputation; diabetic foot; microbial profile; necrotising soft tissue infections; source control
    DOI:  https://doi.org/10.1111/iwj.71045
  43. Microorganisms. 2026 Aug 24. pii: 1882. [Epub ahead of print]14(9):
    Hydrogels for Local Drug Delivery in Biofilm-Associated Periprosthetic Joint Infection: Current Progress and Future Directions.
    Karolina Kraus, Paweł Mikziński, Bindu Subhadra, Emil Paluch.
      Periprosthetic joint infection (PJI) remains one of the most serious complications of arthroplasty, largely due to the formation of microbial biofilms on implant surfaces. Biofilm-associated infections exhibit increased tolerance to antimicrobial therapy and host immune responses, making eradication difficult and often requiring repeated surgical interventions. Consequently, there is a growing need for effective local therapeutic strategies capable of delivering high concentrations of antimicrobial agents directly to the site of infection while minimizing systemic toxicity. Hydrogels have emerged as promising drug delivery platforms for the management of biofilm-associated PJI. Their biocompatibility, injectability, high water content, and tunable physicochemical properties enable controlled and localized release of therapeutic agents within the infected peri-implant environment. This narrative review summarizes recent advances in hydrogel-based approaches, including antibiotic-loaded hydrogels, systems incorporating anti-biofilm enzymes, bacteriophage-loaded formulations, and nanoparticle-enhanced platforms. It also highlights future research directions, with particular emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Particular attention is given to stimuli-responsive ("smart") hydrogels that release therapeutic payloads in response to infection-related triggers such as pH changes, with emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI.
    Keywords:  anti-biofilm enzymes; antibiotic-loaded hydrogels; biofilm infections; hydrogels; nanoparticle-loaded hydrogels; periprosthetic joint infection; phage therapy; smart hydrogels
    DOI:  https://doi.org/10.3390/microorganisms14091882
  44. Mil Med. 2026 Sep 20. pii: usag428. [Epub ahead of print]
    Multidrug-Resistant Organisms in Combat-Related Injuries: Insights from Iraq, Afghanistan, Ukraine, and Implications for Large-Scale Combat Operations.
    Rena Patierno, Elwood Conaway, Marcelo A F Riberio.
       INTRODUCTION: Armed conflict is a powerful driver of antimicrobial resistance, and combat-related infections caused by multidrug-resistant organisms (MDROs) have emerged as a defining challenge of modern military trauma care. Reports from Iraq, Afghanistan, and the ongoing conflict in Ukraine document a clear progression from multidrug-resistant to extensively drug-resistant (XDR) and pan-drug-resistant (PDR) pathogens. This review synthesizes current evidence on combat-related MDRO infections during large-scale combat operations (LSCO) and prolonged field care (PFC).
    METHODS: A narrative literature review was conducted using MEDLINE/PubMed for English-language publications from January 2008 through April 2026, combining the terms war, armed conflict, combat injury, Iraq, Afghanistan, Ukraine, antimicrobial resistance, and multidrug-resistant organisms. Eligible sources included peer-reviewed original research, systematic and narrative reviews, and military clinical guidelines. Standard consensus definitions were used for MDR, XDR, and PDR.
    RESULTS: Combat-related infections are predominantly polymicrobial and dominated by Gram-negative bacilli, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales. The Trauma Infectious Disease Outcomes Study (TIDOS) demonstrated MDR Gram-negative infection in approximately 27% of infected casualties from Iraq and Afghanistan. Surveillance from Ukraine reveals a qualitative escalation: meropenem resistance reaches 72% in A. baumannii and 83%-91% in K. pneumoniae, with co-production of NDM-1, OXA-48, and KPC-2 carbapenemases, frequent resistance to last-line agents (cefiderocol, ceftazidime-avibactam), and convergence of resistance and hypervirulence in international high-risk clones. Frontline wound cultures suggest that MDR acquisition is predominantly nosocomial, occurring along the evacuation chain rather than at the point of injury. Repatriation of foreign combatants colonized by XDR organisms now represents an unprecedented international dissemination risk.
    CONCLUSIONS: The MDRO burden in combat casualties is escalating in scale and severity, with direct implications for LSCO and PFC. Mitigation requires standardized antimicrobial protocols across Role 1 and Role 2 levels of care, centralized oversight by the Defense Health Agency, deployable rapid diagnostics, robust stewardship and infection-prevention programs, and resilient logistics-including drone-enabled medical resupply-to maintain antimicrobial effectiveness and operational readiness.
    DOI:  https://doi.org/10.1093/milmed/usag428
  45. Front Microbiol. 2026 ;17 1892814
    Artificial intelligence applications in biofilm research: computational approaches for biofilm analysis and antimicrobial prediction.
    Jamil Allen G Fortaleza, Kevin Smith P Cabuhat, Edison D Ramos, Jowi Tsidkenu P Cruz, Joel G Matamis, Jose Edwardo R Mamaat, Amelda C Libres, Carlos S de Leon, Jose Jurel M Nuevo.
      Biofilms are organized groups of microbes surrounded by an extracellular polymeric substance (EPS) matrix. This structure helps microbes survive, creates metabolic differences, and makes them less sensitive to antimicrobial treatments. Because biofilms can block antimicrobials and help microbes adapt, they often cause chronic and recurring infections that are hard to treat with standard methods. Most current diagnostic and antimicrobial testing methods focus on free-floating (planktonic) microbes and do not reflect the complex structure and behavior of mature biofilms. This gap often leads to ongoing treatment failures and poor predictions of treatment outcomes. Recently, artificial intelligence (AI) and computational modeling have shown promise for improving biofilm research. These tools can help with automated detection, structural analysis, computational phenotyping, and predicting how biofilms will respond to treatments. This review examines current and emerging AI-based methods in biofilm biology, focusing on computational analysis, prediction of antimicrobial responses, and AI-supported antibiofilm therapies. It also discusses challenges such as dataset differences, limited real-world testing, difficulty understanding models, and a lack of models for clinically important mixed-species biofilms. Overall, this review shows how AI could help improve the accuracy, integration, and tailoring of biofilm research and antimicrobial management.
    Keywords:  artificial intelligence; biofilm-associated infections; machine learning; predictive microbiology; predictive modeling
    DOI:  https://doi.org/10.3389/fmicb.2026.1892814
  46. Niger Med J. 2026 Sep-Oct;67(5):67(5): 1691-1702
    Revascularization Gaps in Diabetic Foot Disease in Nigeria: Health-System Constraints and the Need for a National Limb-Salvage Strategy.
    Oladimeji Adedeji Junaid.
       Background: Diabetic foot ulceration remains a major cause of non-traumatic lower-limb amputation, disability, prolonged hospitalisation and excess mortality. Nigerian studies document substantial burdens of ulceration, late presentation and amputation, but national data on vascular assessment, referral and revascularization remain limited.
    Methodology: PubMed/MEDLINE, Google Scholar and African Journals Online, together with relevant guideline, epidemiology, health-financing and programme websites, were searched from inception to 15 July 2026. Approximately 250 potentially relevant records were identified; about 74 full-text articles, guidelines and policy documents were assessed, and 36 sources were retained for thematic synthesis. Nigerian evidence was prioritised. Selection considered direct relevance, methodological clarity and contribution to prespecified clinical and health-system themes; no formal risk-of-bias instrument or meta-analysis was used.
    Results: The available literature is consistent with a probable, but currently unquantified, revascularization gap within Nigerian diabetic-foot services. Potential contributors include delayed recognition of peripheral arterial disease (PAD), inconsistent objective perfusion assessment, scarce and geographically concentrated vascular expertise, limited imaging and procedural infrastructure, fragmented referral pathways and high out-of-pocket costs. Revascularization remains the central focus of this review because restoration of perfusion is indispensable when ischaemia threatens healing; however, it is one component of comprehensive multidisciplinary care in diabetic foot disease.
    Conclusion: Nigeria should strengthen objective vascular assessment and timely access to revascularization within an integrated limb-salvage pathway that also prioritises infection control, offloading, glycaemic and cardiovascular risk optimisation, wound care, nutrition, smoking cessation and rehabilitation. National data systems are needed to quantify service gaps and evaluate outcomes.
    Keywords:  Nigeria; amputation; diabetic foot ulcer; health financing; limb salvage; peripheral arterial disease; revascularization.
    DOI:  https://doi.org/10.71480/nmj.v67i5.1682
  47. Microorganisms. 2026 Aug 29. pii: 1913. [Epub ahead of print]14(9):
    The Oral and Nasal Gateway Microbiomes: Salivaomics and Systemic Health at the Airway-Digestive Interface.
    Mark L Cannon, John Peldyak, Paul R Reynolds, Gustavo Ferrer.
      The oral cavity is a mucosal and mineralized interface shared by the digestive tract and the upper airway. This narrative review proposes the oral-nasal gateway microbiome as a clinically useful model for understanding oral, nasal, and systemic health. The model includes bacteria, fungi, archaea, protozoa, viruses, bacteriophages, microbial metabolites, and host-derived salivary components. Its gateway role is supported by anatomy, continuous salivation, periodontal vascular exposure, oral-gut microbial overlap, nitrate-nitrite-nitric oxide biology, oral and nasal airway interactions, maternal-child microbial transmission, and enrichment of oral organisms in selected distal diseases and tumors. Oral communities respond rapidly to diet, salivary flow, airway physiology, smoking and vaping, xerostomic medications, antibiotics, and antiseptic rinses, and these changes may influence the nasal microbiome. Published evidence summarizes bacterial pathobionts and protective commensals; Candida and other oral fungi; herpesviruses; papillomaviruses; bacteriophages; salivaomics; pregnancy and early-life prevention; probiotics; polyols; remineralization chemistry; environmental exposures; and tumor microbiology. As of manuscript preparation, SalivaDB catalogs 15,821 salivary biomarker entries across 201 diseases and 48 disease categories. The practical endpoint is not sterilization of the oral cavity but restoration of microbial homeostasis, salivary competence, airway stability, dietary balance, and biologically informed, timely prevention.
    Keywords:  maternal–child health; nasal microbiome; obstructive sleep apnea; oral microbiome; oral–gut axis; oral–nasal airway axis; oral–systemic health; periodontitis; salivaomics; xylitol
    DOI:  https://doi.org/10.3390/microorganisms14091913
  48. BioTech (Basel). 2026 Aug 24. pii: 72. [Epub ahead of print]15(4):
    Bacteriophages 6phi8, 6phi10, and 6phi13 Isolated from the Therapeutic Cocktail "Sextaphag®".
    Vladislav Kulyabin, Andrey Shadrin.
      The present study provides the physicochemical and genomic characterization of three Escherichia bacteriophages (6phi8, 6phi10, and 6phi13) isolated from the commercial phage preparation "Sextaphag®". For each bacteriophage, lytic activity against E. coli MG1655, as well as pH and thermal stability, were determined. Whole-genome sequencing was performed, followed by bioinformatic annotation and comparative genomic analysis. Bacteriophages 6phi8 and 6phi13 belong to the T4-like myoviruses with large genomes (~169 and ~171 kb, respectively), whereas 6phi10 is a T7-like podovirus with a genome size of 40.1 kb. Phage 6phi8 was assigned to the genus Mosigvirus of the family Straboviridae, 6phi13 was classified within the genus Tequatrovirus of the same family, and 6phi10 was identified as a putative novel species of the genus Berlinvirus within the family Autotranscriptaviridae. The genomes of the studied phages lack genes associated with the lysogenic cycle, as well as virulence and antibiotic resistance determinants. The results expand current knowledge of the genomic properties of phages included in therapeutic cocktails and may contribute to the development of phage preparations against infections caused by E. coli and other members of the family Enterobacteriaceae.
    Keywords:  Escherichia spp.; antimicrobial resistance (AMR); bacteriophages; genome
    DOI:  https://doi.org/10.3390/biotech15040072
  49. Front Dent Med. 2026 ;7 1930049
    Periodontitis and Alzheimer's disease, common pathways in down syndrome.
    Fabio Arriola-Pacheco, Alicia Leonor Pinzón-Té, Rodrigo Serrano-Piña, Bertha Arelly Carrillo-Ávila, Jaime Díaz-Zúñiga, Samanta Melgar-Rodríguez, Víctor Manuel Martínez-Aguilar.
      Down Syndrome (DS) involves widespread systemic issues, including a near-universal development of early-onset Alzheimer's Disease, driven by factors beyond Amyloid Precursor Protein (APP) over-expression, such as chronic neuroinflammation and endosomal dysfunction. High prevalence of periodontitis in this population acts as a significant source of peripheral inflammation that may accelerate this cognitive decline, necessitating further study into the bidirectional, pro-inflammatory links between systemic health and neurodegeneration in DS. This review analyzes the common pathophysiological pathways linking periodontitis and AD development within the DS population, evaluating how oral dysbiosis acts as a systemic driver of neurodegeneration. We synthesized current molecular, microbiological, and clinical evidence evaluating the bidirectional relationships between trisomy 21-induced immune dysfunction, severe periodontitis, and accelerated cognitive decline. Individuals with DS exhibit a heightened susceptibility to aggressive, early-onset periodontitis starting as early as age six. This chronic oral dysbiosis facilitates microbial translocation, allowing periodontal pathogens (e.g., Porphyromonas gingivalis) and their virulence factors to cross the blood-brain barrier via circulatory or trigeminal routes. In the central nervous system, these pathogens encounter microglial populations already genetically primed by trisomy 21. This induces an exacerbated M1 microglial phenotype response, triggering sustained neuroinflammation, defensive over-deposition of Amyloid-β (Aβ) plaques, and upregulation of GSK-3β, which accelerates Tau protein hyperphosphorylation. While bidirectional links are strongly indicated, current literature lacks robust longitudinal studies connecting periodontal, microbiological, and cognitive data to establish definitive causality. Early clinical intervention and management of gum disease present a critical therapeutic window to delay the onset and slow the progression of AD in this vulnerable population.
    Keywords:  Alzheimer's disease; cytokines; down syndrome; genes; inflammation; periodontitis
    DOI:  https://doi.org/10.3389/fdmed.2026.1930049
  50. Folia Microbiol (Praha). 2026 Sep 24.
    Bacteriophages and polymeric delivery systems: a mapping review.
    Paula Rogovski, Jéssica Sueli Dos Santos Batista, André Luis Fachini de Souza, Gilberto Melo, Bianca da Costa Bernardo Port, Thiago Caon, Felipe Gomes Dallepiane, Ariadne Cristiane Cabral Cruz, Gislaine Fongaro.
      Bacteriophages are viruses that specifically infect bacteria and have emerged as promising agents for bacterial control in human, animal, and environmental fields. On the other hand, their practical application is limited by instability outside the bacterial hosts, which compromises their efficacy. The incorporation of bacteriophages into polymeric materials has been explored as a strategy to protect the viruses from rapid environmental inactivation and, in some cases, to allow controlled release. In this review, association maps provide a broad overview of the main polymers and fabrication approaches used to improve the stability and functionality of bacteriophages for biotechnological applications. A systematic search was performed to identify studies evaluating polymer-bacteriophage composites focusing on polymer types, bacteriophage species and fabrication processes. The results highlight the broad application of alginate and chitosan, mainly associated with ionic gelation technique, targeting bacterial strains including Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. The oral delivery of bacteriophages, wound dressings and food packaging are among the main applications. Data revealed polymer and approaches selection are mainly associated with intended uses of delivery systems and the target bacteria.
    Keywords:  Bacteriophage; Phage; Phage Delivery System; Phage Release; Polymeric; Polymers
    DOI:  https://doi.org/10.1007/s12223-026-01599-8
  51. Front Microbiol. 2026 ;17 1924442
    Metallo-β-lactamase-producing Pseudomonas aeruginosa: epidemiology, diagnostic challenges and therapeutic strategies in the era of MDR/XDR resistance.
    Alessandra Imeneo, Alessandro Capone, Valentina Antonelli, Valentina Perri, Ivano Petriccione, Alessandra Lodi, Carla Fontana, Stefania Cicalini.
       Background: The management of multidrug-resistant (MDR) Pseudomonas aeruginosa has evolved from an antibiotic-centric approach to a mechanism-driven paradigm. Among resistance determinants, metallo-β-lactamases (MBLs) represent a critical challenge due to their ability to hydrolyse most β-lactams and their increasing global dissemination within high-risk clones.
    Methods: This narrative review aims to summarize the epidemiology, diagnostic approaches and therapeutic strategies for infections caused by MBL-producing P. aeruginosa, emphasizing a mechanism-based clinical framework. A PubMed-MEDLINE search was conducted up to 1 June 2026 using the terms "Pseudomonas aeruginosa", "carbapenem resistance", and "metallo-β-lactamase". Relevant studies were selected based on the authors' assessment of methodological quality and clinical relevance.
    Results: P. aeruginosa exhibits multifactorial resistance involving intrinsic mechanisms (efflux pumps, AmpC overexpression, porin loss), adaptive responses and acquired carbapenemases. MBLs, especially VIM, IMP, and emerging NDM variants, are increasingly associated with carbapenem resistance and epidemic high-risk clones (e.g., ST235, ST111). Global epidemiology shows marked geographic variability in prevalence and molecular types. Diagnostic workup remains challenging due to the coexistence of enzymatic and non-enzymatic mechanisms, requiring integrated use of phenotypic antibiotic susceptibility testing (AST), carbapenemase detection assays, molecular diagnostics, and, in selected cases, whole-genome sequencing (WGS). Among treatment, cefiderocol represents the most evidence-supported option for MBL-producing strains. Aztreonam-based combinations offer an alternative treatment option, provided susceptibility is confirmed by synergy testing. Emerging antimicrobials (e.g., taniborbactam-, xeruborbactam-, and zidebactam-containing regimens) and novel strategies such as bacteriophage therapy are regarded as promising alternatives. Evidence for combination therapy remains limited and should be individualized.
    Conclusions: MBL-producing P. aeruginosa requires an integrated, mechanism-based diagnostic and therapeutic strategy incorporating local epidemiology, rapid diagnostics and optimized antimicrobial selection. Ongoing development of novel agents and precision microbiology tools is expected to further refine clinical management.
    Keywords:  Pseudomonas aeruginosa; carbapenem resistance; cefiderocol; difficult to treat; metallo beta lactamase (MBL)
    DOI:  https://doi.org/10.3389/fmicb.2026.1924442
  52. Pharmaceutics. 2026 Sep 10. pii: 1136. [Epub ahead of print]18(9):
    Antibiotic-Free Strategies for Managing Antimicrobial-Resistant Infections.
    Payal Ganguly, Elena A Jones, Peter V Giannoudis, Giuseppe Tronci.
      Antimicrobial resistance (AMR) presents a global health challenge that is projected to cause nearly 2 million deaths annually by 2050. With a growing ageing population and the rise of antibiotic-resistant strains globally, developing effective alternatives to combat infections while reducing AMR risks is critical. Over recent decades, antibiotic-free strategies have emerged as promising approaches, offering advantages over traditional antibiotics and reducing the likelihood of resistance. This review highlights antibiotic-free antimicrobial strategies for applications in chronic wound care, hard tissue repair, personal protective equipment, as well as hospital hygiene and infection control. We begin by outlining the broader AMR problem and then examine natural strategies-including the use of agents such as manuka honey-followed by synthetic approaches involving nanomaterials and metal-organic frameworks (MOFs), as well as biological and bioinspired antimicrobial strategies, involving antimicrobial peptides, antibodies, bacteriophages, extracellular vesicles, and macrocycles. Finally, we discuss innovations in artificial intelligence (AI)-assisted antimicrobial development and stimulus-responsive materials, before introducing a conceptual design framework for antibiotic-free antimicrobial materials. This review provides a comprehensive assessment of emerging antibiotic-free strategies to guide the development of next-generation antimicrobial solutions that reduce reliance on antibiotics and mitigate AMR in clinical and healthcare settings.
    Keywords:  antibiotic-free strategies; antimicrobial resistance (AMR); infection management; metal–organic frameworks (MOFs); nanoparticles (NPs); natural antimicrobials; polymers
    DOI:  https://doi.org/10.3390/pharmaceutics18091136
  53. Pathogens. 2026 Sep 15. pii: 977. [Epub ahead of print]15(9):
    A Biological Approach to Antimicrobial Resistance in New and Old Bacterial Pathogens.
    Robert J Atterbury, Adriano M Gigante, Paul A Barrow.
      Resistance to antimicrobials in bacterial pathogens has become a major global public health issue that international institutions are now realizing must be tackled with a degree of urgency. A major issue is the self-transmissibility of the plasmids that carry most of the resistance genes. Scientists are now exploring ways in which the antimicrobial resistance plasmids might be tackled directly to reduce resistance. Pharmacological approaches to destabilizing plasmids have not yet been tested in vivo. Phagemids may be used to introduce genes which harm the bacteria themselves or disrupt key plasmid genes. The transfer of transmissible plasmids is mediated by thin conjugative pili which are also attachment sites for a range of lytic bacteriophages. Such phages may be used to kill bacterial cultures where fimbriae are highly de-repressed. They also select for the small number of bacterial cells which have spontaneously lost their plasmid, thereby replacing an antibiotic-resistant strain with one which is once again fully susceptible to antibiotics. This has been demonstrated both in vitro and in animal models of infection. A pharmaceutical approach is proposed to de-repress the plasmids possessed by many strains and thereby increase phage susceptibility.
    Keywords:  antibiotic resistance; antibiotics; antimicrobial resistance; bacteriophage; plasmid
    DOI:  https://doi.org/10.3390/pathogens15090977
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