bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–09–13
27 papers selected by
Luca Bolliger, lxBio



  1. J Chromatogr A. 2026 Aug 30. pii: S0021-9673(26)00730-2. [Epub ahead of print]1787 467404
      The rising rates of antimicrobial resistance (AMR) have become a significant concern, especially as untreatable infections spiral out of control. This has opened new opportunities for developing novel therapeutic approaches. The therapeutic application of phage therapy, utilizing bacteriophages, has gained importance for combating multidrug-resistant (MDR) pathogens, either as an adjuvant or as an alternative to antibiotics. This review evaluates recent advancements in bacteriophage purification technologies in the context of phage therapy against antibiotic resistance, including their modes of action, prospective pharmacology, host ranges, and co-evolution with bacteria. We have also reviewed conventional and emerging bacteriophage purification techniques that aim to enhance the therapeutic potential of bacteriophages, including microfluidics, aqueous two-phase systems, monolithic columns, and chromatography-based membrane systems for endotoxin removal, to improve contaminant removal while maintaining phage infectivity and structural integrity. These modern and efficient purification strategies are being upgraded as a framework towards highly specific, reliable, scalable, and regulatory-compliant purification platforms. Such advancements aim to facilitate the removal of endotoxins, cell debris, and other impurities while preserving phage infectivity and structural integrity. These components are of great importance for the provision and clinical translation of phage therapy, as there is an urgent need for an efficient purification strategy to ensure high-grade purity, safety, and consistency of phage preparations. We also outline the primary associated challenges of phage resistance, immunogenicity, and manufacturing standardization that hinder the development of phage therapy. While there are hurdles to overcome, the use of phages has the potential to form an integrated approach to personalized medicine in addressing antibiotic-resistant strains in the post-antibiotic era.
    Keywords:  Antimicrobial resistance; Bacteriophage purification; Conventional approaches of purification; Emerging purification approaches; Phage Therapy
    DOI:  https://doi.org/10.1016/j.chroma.2026.467404
  2. Vet Microbiol. 2026 Sep 02. pii: S0378-1135(26)00346-9. [Epub ahead of print]322 111209
      Bovine mastitis is one of the most economically burdensome diseases in the global livestock industry. With the growing threat of antimicrobial resistance and the implementation of policies aimed at reducing or prohibiting antibiotic use, the development of novel antimicrobial strategies is urgently needed. Phage therapy, as a biological approach capable of precisely lysing pathogenic bacteria, holds promise as an alternative to antibiotics. This review systematically examines the scientific foundations of phage therapy, covering the phage life cycle, host recognition mechanisms, and the ability to degrade biofilms via depolymerases. It highlights the development strategies of phage cocktails, phage-based combination therapies, and preliminary evidence from preclinical models (e.g., mice) and limited bovine trials demonstrating the potential of phages in reducing bacterial load and alleviating inflammation. Key challenges are also discussed, including insufficient understanding of phage-host interactions within the complex mammary microenvironment, bottlenecks in phage preparation and formulation, the emergence of bacterial resistance, and the absence of a regulatory framework. Finally, this review outlines future research directions, emphasizing the potential of interdisciplinary strategies that integrate artificial intelligence-driven phage screening and rational design, nanomaterials, CRISPR-based gene editing, and novel delivery systems. By systematically summarizing concrete case studies and lessons learned from the clinical translation of phage therapy for bovine mastitis, with a particular focus on formulation engineering and delivery strategies applicable to livestock settings, this review provides a practical roadmap for advancing phage therapy from the laboratory to the farm.
    Keywords:  Antibiotic Alternatives; Bacteriophage Therapy; Bovine Mastitis; Phage Cocktail
    DOI:  https://doi.org/10.1016/j.vetmic.2026.111209
  3. Front Cell Infect Microbiol. 2026 ;16 1897057
      The rapid global expansion of antimicrobial resistance (AMR) threatens to undermine decades of progress in infectious disease management and highlights the limitations of conventional antibiotic-centered therapeutic strategies. Although emerging technologies-including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, microbiome therapeutics, anti-virulence approaches, nanotechnology-enabled drug delivery, and artificial intelligence (AI)-have individually demonstrated considerable promise, they are predominantly being developed as independent interventions rather than as coordinated components of an integrated therapeutic strategy. This Perspective proposes the Intelligent Anti-Infective Ecosystem (IAIE) as a conceptual systems-level framework that computationally integrates multimodal diagnostics, pathogen genomics, microbiome profiling, AI-assisted decision support, programmable precision therapeutics, ecological monitoring, and longitudinal clinical feedback within a continuously learning dynamically optimized workflow. Unlike existing paradigms that primarily optimize individual technologies or therapeutic decisions, IAIE emphasizes closed-loop coordination among complementary antimicrobial approaches to support precision-guided infection management while preserving microbiome integrity and mitigating resistance selection pressure. We further outline the core components, operational principles, translational challenges, and technology readiness of the major therapeutic platforms that could contribute to such an ecosystem, while distinguishing clinically established interventions from emerging experimental strategies. Importantly, IAIE should be interpreted as a prospective conceptual architecture rather than an existing clinical platform. Its proposed clinical value remains to be established through sequential computational, preclinical, and prospective clinical investigations using standardized microbiological, ecological, and patient-centered outcome measures. By framing antimicrobial innovation within an responsive systems perspective, IAIE provides a roadmap for future multidisciplinary research aimed at integrating artificial intelligence and systems microbiology to enable sustainable management of antimicrobial resistance.
    Keywords:  CRISPR antimicrobials; One Health; antimicrobial peptides; antimicrobial resistance; artificial intelligence; bacteriophage therapy; microbiome therapeutics; nanotechnology
    DOI:  https://doi.org/10.3389/fcimb.2026.1897057
  4. J Oral Microbiol. 2026 ;18(1): 2726627
       Background: Periodontitis is a chronic inflammatory disease affecting more than 50% of the global population, resulting in irreversible gum damage, alveolar bone loss and ultimately tooth loss. Periodontitis arises from stable, multi-species biofilms whose pathogenicity is driven by emergent ecological interactions persistent to antimicrobial perturbations. Fusobacterium spp. are considered key microbial components that provide scaffolding for this ecological niche, which includes the pathobionts Tannerella forsythia, Prevotella intermedia and Porphyromonas gingivalis.
    Objectives: To examined how oral microbial interactions shape periodontal biofilms and whether selectively targeting Fusobacterium polymorphum by bacteriophages can disrupt this pathogenic community structure.
    Materials and methods: In vitro biofilms were established using (i) F. polymorphum, T. forsythia and P. intermedia on their own, (ii) T. forsythia and P. intermedia in dual-species biofilms with F. polymorphum and (iii) four-species complex biofilms involving F. polymorphum, T. forsythia, P. intermedia and P. gingivalis. The biofilms were then exposed to the F. polymorphum-specific bacteriophage FNU1 to assess the ecological impact of targeted viral predation on a single member of the biofilm community. Biofilm formation, spatial organisation and microbial interactions were visualised by confocal laser scanning microscopy using CellTrace™ proliferation assays and live-dead staining. Community biofilm biomass was quantified using 0.1% crystal violet staining.
    Results: Multi-species biofilms displayed enhanced biomass and increased cell density relative to simpler communities. Disruption of F. polymorphum by bacteriophage FNU1 led to significant reductions in total biofilm biomass and altered cell density in the single-species F. polymorphum biofilm as well as dual- and four-species complex biofilms.
    Conclusion: Our findings support a role for F. polymorphum-specific bacteriophages in destabilising complex biofilms of periodontal pathobionts. They highlight the importance of F. polymorphum in community dynamics in microbial biofilms and that its precision targeting results in ecological perturbation with the potential to reverse dysbiosis in chronic inflammation in periodontitis.
    Keywords:  Phage therapy; anaerobic pathobionts; microbiota modulation; oral dysbiosis; polymicrobial interactions
    DOI:  https://doi.org/10.1080/20002297.2026.2726627
  5. J Control Release. 2026 Sep 05. pii: S0168-3659(26)00739-X. [Epub ahead of print] 115335
       BACKGROUND: Localized biofilm-associated infections such as chronic wounds, osteomyelitis, and implant infections remain difficult to treat with systemic antibiotics amid rising resistance. Hydrogel delivery may enhance bacteriophage (phage) therapy by protecting phages, prolonging residence, and enabling controlled release. This systematic review summarizes in vivo evidence for hydrogel-mediated phage delivery and its translational relevance.
    METHODS: Following PRISMA 2020, PubMed, Web of Science were searched to 14 January 2026 using MeSH terms for bacteriophages, hydrogels/local delivery, and in vivo or clinical applications. Eligible studies reported original in vivo animal or human data; in vitro-only work was excluded.
    RESULTS: Nineteen studies met criteria: three clinical and sixteen preclinical. Clinical use included fracture-related, burn wound, and prosthetic joint infections treated with commercially available phage preparations in hydrogels. In a single compassionate-use fracture-related infection case managed with concurrent surgical debridement and systemic antibiotics, infection control without recurrence and good bone healing were observed at one year; locally applied phages remained detectable for approximately 72 h, indicating in vivo release and surgical compatibility, although the independent contribution of the hydrogel-phage component could not be isolated. Preclinical studies tested 28 phages against six bacterial species via topical, injected, intraoperative, oral, or irrigation delivery. Consistent benefits occurred in burn (n = 6) and wound/soft-tissue models (n = 5) with lower bacterial load, improved healing, and increased survival in two burn studies. Bone/joint models (n = 4) showed partial reduction but inconsistent eradication. Other studies demonstrated ~2000-fold pathogen reduction in colitis and decreased bacterial and inflammatory markers in endodontic infection.
    CONCLUSIONS: Hydrogel-based local phage therapy is a feasible strategy for infection control No major adverse effects were reported in the included studies, although safety reporting was limited. Standardized in vivo comparisons and clinical trials are needed to optimize delivery and dosing.
    Keywords:  Antimicrobial resistance; Bacteriophages; Controlled release; Hydrogel; Infection; Local delivery
    DOI:  https://doi.org/10.1016/j.jconrel.2026.115335
  6. Infez Med. 2026 ;34(3): 324-333
       Background: The increasing prevalence of antimicrobial resistance (AMR) has created an urgent need for alternative therapeutic strategies. Acinetobacter baumannii, a major cause of hospital-acquired infections, has been classified by the World Health Organization as a critical priority pathogen due to its high levels of multi-drug resistance. Bacteriophage therapy has re-emerged as a potential approach to combat infections caused by multidrug-resistant organisms.
    Methods: Fifty multidrug-resistant (MDR) A. baumannii clinical isolates were collected. Bacteriophages were isolated from hospital sewage using standard enrichment protocols and screened for lytic activity against these isolates using spot and plaque assays. Morphological characterization of purified phages was performed using transmission electron microscopy.
    Results: Three bacteriophages - vB_AbaS_SRNAIIMS002, vB_AbaS_SRNAIIMS008, and vB_AbaP_SRNAIIMS010 - were isolated and demonstrated lytic activity against MDR A. baumannii. Plaque assays revealed clear central zones with surrounding halos, indicating active bacterial lysis. Host range testing showed that two phages exhibited activity against multiple clinical isolates, whereas one displayed a narrow host range. Transmission electron microscopy revealed that two phages belonged to the family Siphoviridae, whereas one was morphologically consistent with the family Podoviridae.
    Conclusions: This study reports the isolation and characterization of three bacteriophages active against MDR A. baumannii. These findings highlight the feasibility of isolating lytic phages from environmental sources and support further investigation of bacteriophage therapy as a complementary strategy to address infections caused by multidrug-resistant pathogens.
    Keywords:  Acinetobacter baumannii; Bacteriophage therapy; antimicrobial resistance; multidrug resistance; phage isolation
    DOI:  https://doi.org/10.53854/liim-3403-6
  7. Plast Reconstr Surg Glob Open. 2026 Aug;14(8): e7974
      Breast implant infection and capsular contracture remain significant complications of implant-based breast surgery, largely driven by bacterial biofilm formation. Despite adherence to perioperative antibiotic prophylaxis and pocket irrigation protocols, established biofilms are difficult to eradicate and frequently necessitate implant removal, resulting in reconstructive, psychological, and financial consequences for patients. In the context of rising antimicrobial resistance and the limited efficacy of antibiotics against biofilm-associated bacteria, bacteriophage therapy has emerged as a biologically compelling adjunctive strategy. Bacteriophages are viruses that selectively infect and lyse bacteria, with a demonstrated capacity to penetrate biofilms and disrupt structured microbial communities. Encouraging clinical outcomes have been reported in orthopedic prosthetic joint infections and vascular graft infections, where phage therapy, often combined with antibiotics, has achieved high rates of bacterial eradication and implant salvage. However, its application in implant-based breast surgery remains largely unexplored, with evidence currently limited to a single experimental study. This translational perspective reviews the biological rationale for bacteriophage use in breast implant-associated biofilm, examines parallels from other implant specialties, and outlines potential preventive and therapeutic applications within breast surgery. Key barriers, including regulatory challenges, phage specificity, delivery strategies within the implant pocket, immune considerations, and the potential emergence of phage resistance, are critically discussed. Bridging this translational gap will require implant-specific biofilm models, standardized delivery protocols, and early-phase clinical evaluation. Bacteriophage therapy represents a promising yet underdeveloped strategy that may expand future options for implant infection management and salvage and, potentially, capsular contracture prevention.
    DOI:  https://doi.org/10.1097/GOX.0000000000007974
  8. Virulence. 2026 Sep 09. 2732318
      Phage resistance represents a major obstacle to the clinical application of phage therapy for multidrug-resistant bacterial pathogens. A comprehensive understanding of the phenotypic heterogeneity and molecular mechanisms underlying phage resistance is critical for deciphering bacterium-phage interactions and optimizing therapeutic strategies. In this study, we identified four distinct resistance phenotypes in K2-serotype hypervirulent carbapenem-resistant Klebsiella pneumoniae (CR-hvKP) under the selective pressure of phage Kpph1. These resistant strains exhibited either complete or partial resistance, variable fitness costs, and diverse genetic mutations, suggesting multifaceted resistance strategies, including receptor masking, growth inhibition, and community-level resistance. Among these, wcaJ mutations were identified as the predominant resistance mechanism, arising from base insertions and integrations of mobile genetic elements, which serve as an efficient pre-adaptive strategy enabling CR-hvKP to evade phage infection. To circumvent this resistance, we isolated a secondary phage, K2V3, which specifically targets wcaJ-mutant strains. The rationally designed phage cocktail comprising Kpph1 and K2V3 effectively suppressed all resistant variants and prevented the emergence of further resistance. Collectively, these findings deepen the understanding of phage-bacteria interaction dynamics and provide a crucial theoretical foundation for optimizing clinical phage therapy against multidrug-resistant pathogens.
    Keywords:  CR-hvKP; Phage resistance; fitness cost; phage cocktails; wcaj
    DOI:  https://doi.org/10.1080/21505594.2026.2732318
  9. Front Cell Dev Biol. 2026 ;14 1735631
      Bacteriophages, the viruses that infect gut bacteria, are now seen as active members of the intestinal ecosystem rather than passive observers. In type 2 diabetes mellitus (T2DM), growing evidence suggests that the gut phage community changes in several important ways. People with T2DM often have lower phage diversity, more temperate phages, and shifts in bacterial hosts. These changes may spread through the microbial network, affecting gene exchange, bacterial metabolism, and immune activity. Through these pathways, phages may contribute to microbial and immune alterations associated with insulin resistance and the chronic inflammation that characterizes T2DM, even though direct proof of causality is still missing. Diet and metabolic stress also influence how phages behave, including their replication cycles and host preferences. This means that environmental factors can constantly reshape the gut virome and, in turn, affect metabolic health. Recognizing this link moves the focus beyond bacterial imbalance to a broader concept of phage-mediated metabolic dysregulation, in which viruses may represent underrecognized contributors to energy balance and inflammation. Understanding these interactions may reveal new microbial targets and guide the development of phage-based or microbiome-based approaches for the prevention and treatment of T2DM.
    Keywords:  bacteriophage; gut virome; metabolic inflammation; microbial metabolism; phage therapy; type 2 diabetes mellitus
    DOI:  https://doi.org/10.3389/fcell.2026.1735631
  10. New Microbes New Infect. 2026 Oct;73 101837
       Background: Shigella causes severe bacterial diarrhea, especially in children in low- and middle-income countries. Rising antimicrobial resistance (AMR), including multidrug-resistant (MDR) and ESBL-producing strains, threatens empirical treatment, particularly cephalosporins.
    Methods: We conducted a structured narrative review of PubMed, Scopus, Web of Science, ScienceDirect, and WHO GLASS. Included studies comprised randomized trials, cohorts, case series, and relevant in vitro studies. Quality was appraised using Joanna Briggs Institute checklists; findings were synthesized narratively.
    Results: Third-generation cephalosporins (ceftriaxone, cefotaxime) remain highly effective for severe Shigella infections in hospitalized and pediatric patients when isolates are susceptible. Resistance varies regionally, with higher ESBL prevalence in East and South Asia. Resistance mechanisms include ESBLs, efflux pumps, PBP mutations, and altered membrane permeability. Susceptibility-guided therapy yields favorable outcomes, but ESBL/XDR strains cause treatment failures, longer hospital stays, and carbapenem use.
    Conclusion: Cephalosporins are critical for severe shigellosis but are increasingly compromised by AMR. Structured surveillance, susceptibility-guided therapy, and stewardship are essential. Complementary strategies (vaccines, probiotics, phage therapy, novel antibiotics) are urgently needed.
    Keywords:  Antimicrobial resistance; Cephalosporins; Extended-spectrum β-lactamases; Multidrug resistance; Phage therapy; Shigella; Vaccines
    DOI:  https://doi.org/10.1016/j.nmni.2026.101837
  11. Int J Antimicrob Agents. 2026 Sep 11. pii: S0924-8579(26)00291-8. [Epub ahead of print] 108004
      Enterobacter hormaechei, a multidrug-resistant member of the Enterobacter cloacae complex, is an important cause of healthcare-associated infections with limited therapeutic options. Here, we isolated and characterized five strictly lytic phages (ΦEAS1, ΦEHO4B, ΦEHO11, ΦEHO14, and ΦECL22) active against multidrug-resistant E. hormaechei. Transposon sequencing combined with targeted gene knockouts demonstrated that phage infection involved multiple bacterial surface structures, including lipopolysaccharide core oligosaccharides, O-antigen, OmpA, and fimbriae, with one phage showing simultaneous multi-receptor dependence. Despite receptor diversity, certain phage combinations displayed antagonistic interactions, indicating that ecological compatibility, rather than receptor complementarity alone, determines cocktail efficacy. Guided by receptor profiling and interaction screening, an optimized four-phage cocktail lysed 86.4% of clinical isolates and effectively suppressed planktonic growth and biofilm formation in vitro. In a murine bacteremia model, phage treatment achieved 100% survival, outperforming Polymyxin B therapy. These findings demonstrate that receptor-diverse phage cocktails can provide robust therapeutic efficacy, but that inter-phage ecological interactions critically constrain optimal design. This study establishes mechanistic principles for rational phage cocktail optimization against multidrug-resistant E. hormaechei.
    Keywords:  Enterobacter cloacae complex; Enterobacter hormaechei; antagonistic; bacteremia model; phage cocktail; receptor
    DOI:  https://doi.org/10.1016/j.ijantimicag.2026.108004
  12. J Vis Exp. 2026 Sep 08.
      To systematically analyze the research landscape of antimicrobial resistance (AMR) in China from 2016-2025, identify hotspots, and detect emerging trends using bibliometric visualization techniques. We compiled 3,096 publications from the Web of Science Core Collection (including Science Citation Index Expanded, SCI-E) and China National Knowledge Infrastructure (CNKI). Using CiteSpace, we performed co-authorship network analysis, keyword co-occurrence mapping, and cluster analysis employing the Log-Likelihood Ratio (LLR) algorithm. Burst detection via Kleinberg's algorithm identified research frontiers, while modularity Q (>0.3) and silhouette metrics validated network structural quality. Rising from 357 in 2016 to 365 in 2022, with accelerated growth following the 2019-2022 period. Six major research clusters emerged with significant structural validity (modularity Q = 0.8108). Burst analysis identified mobilized colistin resistance-1 (mcr-1, burst strength 9.12) and carbapenemase (8.52) as the strongest emerging signals. Resistance surveillance revealed divergent trends: carbapenem-resistant Klebsiella pneumoniae increased alarmingly from 5.6% to 20.0%, whereas methicillin-resistant Staphylococcus aureus declined from 48.8% to 25.8%. Author network analysis revealed a highly centralized structure with limited cross-regional collaboration. Novel therapeutics, including antimicrobial peptides, phage therapy, and machine learning applications, demonstrated significant emergence. Overall, the bibliometric patterns suggest that AMR research in China has evolved from descriptive surveillance toward mechanistic investigation and increasing attention to innovative interventions. The contrasting decline in methicillin-resistant Staphylococcus aureus and rise in carbapenem-resistant pathogens highlight the need for continued national surveillance, stronger inter-regional collaboration, targeted antimicrobial stewardship, and cautious translation of emerging technologies into clinical practice.
    DOI:  https://doi.org/10.3791/72404
  13. MicroPubl Biol. 2026 ;2026
      The SEA-PHAGES program maintains an extensive archive of student-discovered Actinobacteriophage as a resource for understanding phage diversity. Here, we examine host range of thirty phages isolated on Arthrobacter globiformis B-2979 against additional strains of A. globiformis and against other isolates within ' Arthrobacter sensu stricto '. Consistent with other reports, host range of these phages was generally narrow. A general relationship between magnitude and prevalence was observed in efficiency of plating on globiformis isolates other than the isolation host, suggesting underlying mechanisms of cross-infectivity.
    DOI:  https://doi.org/10.17912/micropub.biology.002306
  14. Bioinformation. 2026 ;22(6): 3300-3304
      Diabetic foot ulcers (DFUs) remain a serious complication of diabetes mellitus, often leading to infection, prolonged hospitalization and potential limb amputation. Therefore, it is of interest to evaluate the outcomes of surgical versus non-surgical management of DFUs in 100 patients, divided equally into two groups of fifty each. Group A received surgical interventions such as debridement and minor procedures, while Group B underwent non-surgical care including dressings, antibiotics, glycemic control and off-loading. Healing progress, infection control, duration of recovery and complication rates was closely monitored. Thus, we show that surgical management yields faster healing and superior infection control in moderate to severe cases, while non-surgical care is suitable for mild ulcers, advancing current understanding of tailored treatment strategies to optimize DFU outcomes.
    Keywords:  Surgical and non-surgical wound; diabetic foot ulcer (DFU); infection
    DOI:  https://doi.org/10.6026/973206300223300
  15. Front Microbiol. 2026 ;17 1934262
      
    Keywords:  antimicrobial resistance; functional genomics; metagenomic diagnostics; mobile genetic elements; novel therapeutics; phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2026.1934262
  16. BMJ Digit Health Ai. 2026 ;2(1): e000069
       Objective: Wounds represent a major global health and economic burden, with chronic wounds affecting millions annually and costing medical care providers over $126 billion in the USA alone. Current assessment tools, such as percent area reduction (PAR), are widely used but limited by subjectivity and suboptimal predictive accuracy, particularly for complex wound types. This study aimed to evaluate the performance of an artificial intelligence (AI)-powered Healing Index (HI) in predicting delayed healing compared with PAR, leveraging the growing integration of AI into healthcare to enhance wound assessment and prognostic capabilities.
    Methods and analysis: This retrospective study evaluated the performance of the AI-powered HI in predicting delayed healing for pressure injuries, venous ulcers, diabetic foot ulcers and arterial ulcers. Using a clinically validated dataset of 173 816 wounds collected via a digital wound care solution, the HI model's predictive accuracy was compared with PAR. The HI incorporated objective wound characteristics, such as tissue composition and exudate, to forecast healing trajectories.
    Results: By week 3, the HI achieved a balanced accuracy of 65%, surpassing PAR, which reached the same level only in week 4. This earlier prediction enables more timely treatment adjustments, facilitating improved outcomes and reducing healthcare costs.
    Conclusion: The AI-powered HI demonstrates significant potential for transforming wound care by providing more accurate, objective and earlier identification of non-healing wounds. Its integration into clinical practice could enhance resource allocation, optimise treatment strategies and reduce the economic burden of chronic wounds. Further validation across diverse healthcare settings is warranted to ensure equitable implementation.
    Keywords:  Artificial intelligence; Machine Learning; Smartphone
    DOI:  https://doi.org/10.1136/bmjdh-2026-000069
  17. Injury. 2026 Sep 05. pii: S0020-1383(26)00669-8. [Epub ahead of print]57(10): 113682
      Fracture related infections (FRI) are a devastating complication of orthopedic trauma care, most commonly caused by Staphylococcus aureus. The organisms' ability to form biofilms complicates conventional antibiotic therapy and drives demands for novel therapeutics. One promising novel approach is bacteriophage therapy, however this therapeutic has a narrow host range. Thus, understanding whether S. aureus FRIs are clonal or polyclonal is crucial for development of bacteriophage therapy. Consequently, the aim, of this study, was to evaluate 15 S. aureus clinical FRI isolates to determine clonality. For each individual FRI, eight colonies underwent whole-genome sequencing and results were compared to a reference strain to determine genomic variants. Isolates from each individual patient demonstrated greater than 92% shared genomic variants and over a 98% overlap with a merged variant profile, indicating clonal infections across all 15 FRIs. Furthermore, we assessed bacteriophage K activity to the planktonic states of the isolates for which there was similar activity against each individual FRI but different activity amongst the 15 FRI isolates. Lastly, we evaluated variations of genes associated with bacteriophage attachment receptors glycosylation (tarS, M, P) in which there were identical sequences across colonies for each individual FRI, indicating limited intra-infection variation in glycosylation potential of this receptor. This data supports that S. aureus FRI are clonal infections which typically have uniform bacteriophage attachment receptor glycosylation profiles within individual infections. These findings are vital for the development of bacteriophage therapy, suggesting that a single S. aureus colony is sufficient to conduct in vitro testing to determine bacteriophage activity to planktonic forms of S. aureus FRI in vivo. Yet further similar studies evaluating sessile heterogeneity are warranted. Nonetheless, the foundation of knowledge seen here supports further translational research and refinement of bacteriophage therapeutic strategies for S. aureus FRI.
    Keywords:  Bacteriophage therapy; Clonality; Fracture-related infections; Glycosylation; Staphylococcus aureus; Wall teichoic acid
    DOI:  https://doi.org/10.1016/j.injury.2026.113682
  18. Diabetology (Basel). 2026 May;7(5): 96
       Background: Smart offloading technologies enable the real-time, objective monitoring of adherence in patients with diabetic foot ulcers (DFUs). Although remote tracking may reinforce adherence and improve wound healing, effectiveness depends on sustained device use, particularly as devices are often removed during rest periods. Real-time, behavior-contingent feedback informed by sensor data, including AI-supported messaging capable of detecting nonadherence, may enhance reinforcement. However, the feasibility and behavioral impact of such strategies remain unclear.
    Methods: We conducted a prospective feasibility case series nested within a larger DFU cohort of 210 participants, enrolling eight adults with active DFUs. Participants used a sensor-integrated offloading device paired with a smartwatch (SmartBoot) and a mobile application (CORA) that delivered notifications to their smartphones. Notifications were either schedule-based or context-aware, using real-time SmartBoot data to generate personalized messages. The primary outcome was a sensor-detected transition from nonadherent to adherent offloading within 60 min.
    Results: A total of 130 notifications were delivered, with 125 included in the behavioral response analysis. Context-aware notifications demonstrated higher transition rates than schedule-based notifications. Adaptive Reinforcement yielded the highest response rate (77.4%, 24/31), followed by Clinical Course Correction (71.4%, 20/28), whereas Safety and Technical Assurance (40.7%, 11/27) and Motivational Coaching (30.8%, 12/39) showed lower response rates.
    Conclusions: Real-time, context-aware feedback is feasible and associated with improved short-term adherence, supporting evaluation in larger trials.
    Keywords:  context-aware notifications; diabetic foot ulcer; feasibility; mobile health; offloading; remote monitoring; wearable sensors
    DOI:  https://doi.org/10.3390/diabetology7050096
  19. Arch Oral Biol. 2026 Sep 06. pii: S0003-9969(26)00268-2. [Epub ahead of print]192 106760
       OBJECTIVE: To investigate gingival crevicular fluid (GCF) levels of stimulator of interferon genes (STING), 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP), and interferon-β (IFN-β) across periodontal health, gingivitis, and periodontitis.
    DESIGN: This study included 180 participants: 45 periodontally healthy individuals, 45 patients with gingivitis, 45 with Stage I-II periodontitis, and 45 with Stage III-IV periodontitis. GCF samples were collected for enzyme-linked immunosorbent assay (ELISA) measurement of STING, 2'3'-cGAMP, and IFN-β.
    RESULTS: GCF STING, 2'3'-cGAMP, and IFN-β levels increased from periodontal health to gingivitis, Stage I-II periodontitis, and Stage III-IV periodontitis. Correlation analysis showed that STING was positively correlated with 2'3'-cGAMP and IFN-β, and 2'3'-cGAMP was positively correlated with IFN-β. Within-group correlations between 2'3'-cGAMP and STING or IFN-β became more evident with increasing periodontal disease severity. In patients with periodontitis, these biomarkers were positively associated with clinical attachment loss to varying degrees. ROC analysis showed that the three-biomarker combined model yielded numerically higher AUCs than the individual biomarkers, with AUCs of 0.886 for distinguishing periodontitis from non-periodontitis and 0.949 for distinguishing Stage III-IV periodontitis from non-periodontitis. DeLong testing showed that statistically significant improvements over individual biomarkers were confined to selected comparisons. After adjustment for age, BMI, sex, and current smoking, higher levels of STING, 2'3'-cGAMP, and IFN-β remained independently associated with worsening periodontal status and increased periodontitis risk.
    CONCLUSION: GCF STING, 2'3'-cGAMP, and IFN-β were positively associated with periodontal disease severity, and their combined detection may serve as an adjunctive biomarker approach for periodontal assessment.
    Keywords:  2′3′-cGAMP; Gingival Crevicular Fluid; IFN-β; Periodontitis; STING
    DOI:  https://doi.org/10.1016/j.archoralbio.2026.106760
  20. Microbiologyopen. 2026 Oct;15(5): e70400
      This study aimed to analyse antimicrobial resistance (AMR) in bacterial isolates from subgingival biofilms of patients with periodontitis and supragingival biofilms of orally healthy individuals, and to explore the association between biofilm-forming capacity and AMR. Three hundred and forty-seven bacterial isolates from 44 patients were analysed. Bacterial isolates were obtained from subgingival/supragingival biofilm and identified using MALDI-TOF mass spectrometry. Antibiotic susceptibility was evaluated by the Kirby-Bauer test, the E-test, and a β-lactamase activity assay, and biofilm formation capacity was assessed using the gentian violet assay. The 44 participants (median age 28.0 [25.0; 55.0]) were stratified into untreated generalised stage III/IV periodontitis (n = 21) and orally healthy (n = 23) groups. Among 347 isolates, 74.4% formed biofilms. AMR was generally higher in isolates from orally healthy subjects (77.7% vs. 59.1% in periodontitis patients, p < 0.001) and females (73.2% vs. 60.6% in males, p = 0.026). Multivariate binary logistic mixed models linked biofilm formation to AMR (OR: 1.66 CI: [1.12, 2.49]; p = 0.045 for severe biofilm formers and OR: 1.93 CI: [1.31, 2.83]; p = 0.004 for moderate biofilm formers). Phenotypic antimicrobial resistance was thus commonly detected throughout the cohort and was at least as frequent in orally healthy participants as in patients with periodontitis. Because the orally healthy group was substantially younger, this contrast is confounded by age and smoking and cannot be interpreted as an independent effect of periodontal status. Furthermore, this study might indicate that biofilm-forming isolates may exhibit increased antibiotic resistance.
    Keywords:  antibiotic resistance; antibiotics; biofilm; periodontitis
    DOI:  https://doi.org/10.1002/mbo3.70400
  21. Proc Natl Acad Sci U S A. 2026 Sep 15. 123(37): e2615890123
      The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.
    Keywords:  Candidate Phyla Radiation; Patescibacteria; bacteriophage; episymbiosis; oral microbiome
    DOI:  https://doi.org/10.1073/pnas.2615890123
  22. Expert Rev Anti Infect Ther. 2026 Sep 08.
       INTRODUCTION: Serious infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) remain a major global challenge, with high morbidity, mortality, and limited therapeutic options. Combination antibiotic therapy has long been proposed as a strategy to improve clinical outcomes, enhance bacterial killing, and prevent antimicrobial resistance, yet its clinical value across key pathogen groups remains uncertain.
    AREAS COVERED: This review summarizes current evidence on combination therapy for major MDR-GNB, including third-generation cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and other non-fermenters. We examine both clinical and preclinical data, reviewing in vitro synergy studies (checkerboard assays, time-kill experiments, and E-tests), randomized controlled trials, major observational studies, and treatment recommendations from international guidelines.
    EXPERT OPINION: Robust clinical evidence supporting combination therapy is limited. Synergy observed in vitro does not reliably translate into improved patient outcomes, and toxicity risks remain important. For most MDR-GNB infections, current data support targeted monotherapy with newer β-lactam/β-lactam-inhibitors agents when active. Combination therapy may retain a role in selected scenarios, including salvage treatment, infections due to metallo-β-lactamase producers, A. baumannii and S. maltophilia, or in settings with limited access to newer agents.
    Keywords:  Carbapenem-resistant enterobacterales; Combination antibiotic therapy; Multidrug-resistant gram-negative bacteria; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; Third-generation cephalosporin-resistant enterobacterales; acinetobacter baumannii; antimicrobial resistance; bloodstream infections; in vitro synergy; randomized controlled trials
    DOI:  https://doi.org/10.1080/14787210.2026.2730311
  23. Front Microbiol. 2026 ;17 1928352
      Methicillin-resistant Staphylococcus aureus (MRSA) wound infections remain a major clinical challenge due to antibiotic resistance and biofilm persistence. Although phage therapy has re-emerged as a promising alternative, its efficacy is limited by poor stratum corneum penetration following conventional topical application. Here, we isolated and characterized a lytic MRSA phage, Pelagios, and evaluated its transdermal delivery using detachable dissolvable microneedles (DDMNs). Genomic analyses classified Pelagios within the genus Silviavirus of the family Herelleviridae and indicated that it may represent a novel species. The phage displayed rapid adsorption (∼15 min), a short latent period (∼20 min), a burst size of ∼102 PFU/cell, and stability across physiologically relevant temperature (4 °C -45 °C) and pH conditions (pH 4-10). Whole-genome sequencing confirmed the absence of toxin genes, virulence factors, antimicrobial resistance determinants, and lysogeny-associated genes, supporting its genomic safety. Pelagios exhibited broad lytic activity against multiple clinical MRSA isolates and significantly reduced planktonic bacterial populations both in vitro and in ex vivo porcine skin models in a dose-independent manner. It also effectively inhibited MRSA biofilm formation, although eradication of established biofilms was limited. Phage-loaded DDMNs fabricated from hyaluronic acid and gelatin achieved efficient skin penetration, rapid dissolution, complete needle detachment, and markedly improved phage stability at 4 °C. In ex vivo infection models, DDMN-mediated delivery significantly enhanced antibacterial and biofilm-eradicating efficacy compared with free phage suspension. These findings demonstrate that Pelagios delivered via DDMNs constitutes a safe and effective strategy for treating MRSA-associated wound and biofilm infections.
    Keywords:  Staphylococcus aureus; biofilms; dissolving microneedles; phage therapy; wound infections
    DOI:  https://doi.org/10.3389/fmicb.2026.1928352
  24. BMJ Public Health. 2026 ;4(3): e004554
       Objectives: To evaluate the association between socioeconomic factors and diabetic foot ulcers (DFUs) among adults with diabetes mellitus through systematic review and meta-analysis.
    Design: Systematic review and meta-analysis of observational studies conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.
    Data sources: PubMed/MEDLINE, Scopus, CINAHL and Google Scholar were systematically searched from database inception to 31 December 2024, with a final updated search performed in February 2025.
    Eligibility criteria: Cross-sectional and case-control studies evaluating the association between socioeconomic factors and DFUs among adults with diabetes mellitus were included.
    Data extraction and synthesis: Study selection and data extraction were performed independently by two reviewers. Methodological quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for cross-sectional studies and the Newcastle-Ottawa Scale for case-control studies. Random-effects meta-analysis was used to pool ORs and corresponding 95% CIs. Heterogeneity was assessed using the I² statistic.
    Results: Eight cross-sectional and case-control studies involving 3488 participants were included. Lower educational attainment was significantly associated with higher odds of DFUs (pooled OR=2.54, 95% CI 1.24 to 5.20; I² = 68.0%). Similarly, lack of formal employment was associated with higher odds of DFUs (pooled OR=1.71, 95% CI 1.05 to 2.77; I² = 21.2%). In contrast, although low income showed increased pooled odds of DFUs, the association did not reach statistical significance under the random-effects model (pooled OR=2.70, 95% CI 0.36 to 20.41; I² = 81.9%). Interpretation of the income analysis was limited by substantial heterogeneity and wide CIs. Sensitivity analyses excluding moderate-to-high risk studies demonstrated similar directions of association for education and occupational status.
    Conclusions: Lower educational attainment and lack of formal employment were associated with higher odds of DFUs among individuals with diabetes mellitus. These findings suggest that socioeconomic factors should be considered in diabetic foot prevention and management strategies alongside conventional clinical risk factors. Further high-quality prospective studies using standardised socioeconomic measures are needed to strengthen the evidence base in this area.
    Keywords:  Confounding Factors, Epidemiologic; Diabetes Mellitus; Social Medicine; Systematic Review
    DOI:  https://doi.org/10.1136/bmjph-2025-004554
  25. Plast Reconstr Surg Glob Open. 2026 Sep;14(9): e8115
      Diabetic foot ulcer (DFU) is one of the most challenging complications of diabetes mellitus. Chronic hyperglycemia contributes to impaired immune function, characterized by failure of macrophage polarization from the proinflammatory M1 to the prohealing M2 phenotype, together with increased release of inflammatory mediators. ON101 is a novel macrophage-regulating topical agent derived from botanical extracts, designed to suppress proinflammatory cytokines, restore M1/M2 macrophage balance, and promote collagen synthesis. We report the case of a 77-year-old man with diabetes mellitus who presented with a chronic, nonhealing ulcer of the right fifth toe with exposed tendon, persisting for 2 years despite conventional wound care and twice-daily Aquacel Ag+ extra dressing changes. The wound was accompanied by local inflammation, whereas angiographic evaluation suggested preserved distal runoff without evidence of critical macrovascular occlusion. ON101 topical therapy was initiated once daily under PolyMen dressing, leading to progressive granulation tissue formation, epithelial coverage of the tendon, and complete wound closure within 2 months. Notably, the total amount of ON101 used throughout the treatment course was less than 1 15-g tube. Given the chronicity of the wound, the presence of exposed tendon, and the difficulty of achieving durable healing in distal diabetic toe ulcers, this case suggests that ON101 may provide substantial therapeutic benefit in selected refractory cases.
    DOI:  https://doi.org/10.1097/GOX.0000000000008115
  26. Expert Rev Anti Infect Ther. 2026 Sep 11.
       INTRODUCTION: Neisseria gonorrhoeae has evolved antimicrobial resistance (AMR) since the first use of antimicrobial treatment of gonorrhea. The AMR development is driven by the bacterium's high capacity for genetic adaptation, antimicrobial overuse and misuse, and insufficient surveillance. Novel therapeutic options are urgently needed.
    AREAS COVERED: This review summarizes novel gonorrhea treatment options, with special emphasis on the novel oral antimicrobials zoliflodacin and gepotidacin that obtained US FDA-approval for treatment of uncomplicated urogenital gonorrhea in December 2025. It also highlights compounds in early clinical or preclinical development that have demonstrated promising in vitro activity against N. gonorrhoeae.
    EXPERT OPINION: Zoliflodacin and gepotidacin have the potential to optimize gonorrhea management as oral alternatives to current injectable ceftriaxone. Their successful long-term use will depend on optimized use strategies, including indications, evidence-based approved dosing, adherence, surveillance, and population-specific considerations. Public-health agencies and clinicians will need to balance broad clinical access with antimicrobial stewardship measures to delay the AMR emergence. Looking ahead, gonorrhea management will hopefully shift from empirical, syndromic treatment toward etiology-guided and AMR-informed therapy, driven by advances in rapid point-of-care testing and whole-genome sequencing technologies. Continuous phenotypic and genomic surveillance remains essential to detect early AMR signals, transmission of AMR strains, and inform treatment guidelines.
    Keywords:  AMR; antimicrobial resistance; debio 1453; gepotidacin; gonorrhea; neisseria gonorrhoeae; resistance; treatment; zoliflodacin
    DOI:  https://doi.org/10.1080/14787210.2026.2733617