bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–10–11
forty papers selected by
Luca Bolliger, lxBio



  1. Front Cell Infect Microbiol. 2026 ;16 1968526
      Chronic pulmonary infections caused by multidrug-resistant (MDR) bacteria are a growing global health problem, and the declining effectiveness of conventional antibiotics increases the need for alternative antimicrobial strategies. Unlike broad-spectrum antibiotics, bacteriophages are highly specific, and their use therefore offers not only antibacterial activity but also the possibility of reshaping the airway microbial ecosystem in a targeted manner. In this review, we reframe phage therapy as a precision microbiome-modulating strategy for chronic pulmonary infections. We first review precision pathogen identification and phage-host matching, then discuss formulation engineering for pulmonary delivery, and then examine the interactions between phages and host immune barriers. We further analyze how phage therapy may selectively deplete MDR pathogens while sparing the commensal microbiota and how it may remodel the airway microbial ecosystem, and we critically evaluate the clinical evidence, distinguishing preclinical data, case-based evidence, observational studies, and controlled trials. By integrating these dimensions, we identify the main scientific and technical challenges and evidence gaps that currently limit clinical implementation, and we discuss strategies that could support the development of safe, effective, and clinically applicable phage-based therapies for chronic pulmonary infections.
    Keywords:  airway microbiome; clinical translation; drug-resistant bacteria; immune regulation; microbiome modulation; phage therapy; pulmonary delivery
    DOI:  https://doi.org/10.3389/fcimb.2026.1968526
  2. Infection. 2026 Oct 03.
       BACKGROUND: Acinetobacter baumannii is a WHO critical-priority pathogen that causes life-threatening healthcare-associated infections, particularly in intensive care units (ICUs). In South Asia and the Middle East, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are common and resistance to cephalosporins is 87-100% and to carbapenems 78-90%, leaving only a few remaining therapeutic options like colistin, tigecycline, and polymyxin B.
    OBJECTIVES: This review aimed to provide an overview of the current knowledge regarding the epidemiology, virulence factors, and resistance mechanisms of MDR/XDR A. baumannii globally and within Pakistan, with particular emphasis on therapeutic approach using bacteriophages as potential alternative to conventional antimicrobial therapy. This review is distinguished from prior publications on A. baumannii phage therapy by its integration of Pakistan-specific epidemiological and phage-isolation data with a critical, comparative synthesis of phage-antibiotic synergy evidence and emerging (2024-2026) clinical and preclinical literature.
    CONTENT: This review synthesizes current isolation, purification, and genomic/proteomic characterization methods for A. baumannii-targeting bacteriophages, and critically evaluates phage-antibiotic synergy (PAS), in vivo and compassionate-use clinical evidence, and translational and regulatory barriers, alongside emerging alternative antimicrobial strategies and surveillance gaps in resource-limited settings such as Pakistan.
    CONCLUSIONS: In conclusion, combination therapy of phage and antibiotics, especially sequential phage-colistin therapy, is a promising strategy against MDR/XDR A. baumannii infections. There are several key priorities for the future to consider, such as the establishment of national phage banks, development of standardized phage susceptibility testing (phagograms), and the integration of phage therapy into antimicrobial stewardship and surveillance frameworks, especially in high-burden, resource-limited settings such as Pakistan.
    Keywords:   Acinetobacter baumannii ; Bacterial; Bacteriophages; Drug resistance; Multiple; Nosocomial infection; Phage therapy
    DOI:  https://doi.org/10.1007/s15010-026-02980-y
  3. J Drug Target. 2026 Oct 09. 1-77
      The rapid emergence of multidrug-resistant (MDR) bacterial infections has intensified the demand for advanced antimicrobial drug delivery strategies capable of improving therapeutic efficacy while overcoming the limitations of conventional antibiotics. Bacteriophage therapy has re-emerged as a promising antibacterial approach because of its high specificity and potent activity against antibiotic-resistant pathogens. Nevertheless, the clinical translation of free bacteriophages remains restricted by multiple biological barriers, including rapid immune clearance, limited retention at infection sites, enzymatic degradation, poor stability, and inadequate penetration into bacterial biofilms. Hydrogel-based drug delivery systems have emerged as versatile biomaterial platforms that effectively address these challenges by protecting bacteriophages from environmental degradation, enabling localized administration, prolonging residence time, and providing sustained and controlled phage release. This review critically discusses the major biological barriers limiting successful bacteriophage therapy and highlights recent advances in hydrogel engineering strategies designed to improve phage encapsulation, stability, release behavior, and antibacterial efficacy. Furthermore, the physicochemical characteristics of hydrogels that influence phage delivery, including biocompatibility, porosity, swelling behavior, degradability, tissue adhesiveness, and mechanical properties, are examined in relation to their effects on phage retention and release. Recent applications of hydrogel-assisted bacteriophage delivery in chronic wound infections, biofilm-associated infections, surgical site infections, and other MDR bacterial diseases are summarized, with particular emphasis on localized antimicrobial therapy. Finally, current challenges related to formulation design, large-scale manufacturing, regulatory approval, and clinical translation are discussed, together with future perspectives for developing clinically applicable hydrogel-based phage delivery systems. Collectively, this review evaluates the current evidence supporting hydrogel-mediated bacteriophage delivery and identifies key considerations for the development and clinical translation of effective localized phage delivery systems against multidrug-resistant bacterial infections.
    Keywords:  Bacteriophage therapy; Biofilm; Controlled release; Drug delivery systems; Hydrogel; Multidrug-resistant bacteria
    DOI:  https://doi.org/10.1080/1061186X.2026.2746044
  4. Front Immunol. 2026 ;17 1904873
      Filamentous bacteriophages, of the family Inoviridae, are characterized by their reproduction and secretion by their bacterial hosts without killing them. These viruses have evolved mutualistic relationships with their bacterial hosts by impacting bacterial phenotypes in a variety of ways, including biofilm formation, horizontal gene transfer, colonization, and motility. Previous studies have reported that filamentous bacteriophages contain virulence factors that promote the pathogenesis of bacterial infections in animal models and are associated with exacerbating infections in humans. Additionally, these phages have been experimentally used as cloning vectors for DNA sequencing, phage display, and nanotechnological applications. Finally, viromic studies have revealed a substantial presence of filamentous bacteriophages in the human gut. However, their interactions with mammalian cells have not been extensively explored. Here, we review the immunogenicity of filamentous bacteriophages in eukaryotic cells. First, we address how filamentous bacteriophages impact the fitness of their prokaryotic hosts. Then, we review their immunogenicity by focusing on the direct interactions between filamentous bacteriophages and eukaryotic cells that may indicate how these viruses influence various functions. Finally, we provide some thoughts on their impact for use in therapeutics. Through their ubiquitous interactions with prokaryotic and eukaryotic cells, there is still much to be learned about how filamentous bacteriophages affect the biology, pathogenesis, and physiology of the human gut. Unraveling these interactions will provide further evidence as to the importance of the virome to human health.
    Keywords:  Inoviridae; adaptive immunity; bacteriophage; bacteriophage–host interactions; filamentous; immunogenicity; immunomodulation; innate immunity
    DOI:  https://doi.org/10.3389/fimmu.2026.1904873
  5. Microb Pathog. 2026 Oct 08. pii: S0882-4010(26)00597-8. [Epub ahead of print] 108871
      Antimicrobial resistance (AMR) has emerged as one of the most severe global health threats. The rapid expansion of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens compromises the effectiveness of conventional antibiotics. Globally, ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have led to therapeutic failure, prolonged hospitalization, and increased mortality rates. This review identifies the molecular mechanisms, including enzymatic antibiotic inactivation, efflux pump overexpression, biofilm formation, and horizontal gene transfer, that underline the resistance of disseminated pathogens to antibiotics in clinical, agricultural, and environmental settings. Antibiotic overuse and pharmaceutical and agricultural discharges create persistent reservoirs for the dissemination of AMR genes. Furthermore, we evaluated the non-traditional antibacterial efficacy of antimicrobial peptides, bacteriophage therapy, monoclonal antibodies, probiotics, fecal microbiota transplantation, anti-virulence agents, CRISPR-Cas precision antimicrobials, and nanotechnology-based drug delivery platforms. Current preclinical and clinical evidence indicates the eradication of resistant pathogens, disruption of biofilms, and preservation of host microbiota, thereby reducing the selective pressure associated with broad-spectrum antibiotics. Despite these advances, major translational barriers, such as pharmacokinetic instability, manufacturing limitations, and insufficient clinical validation, restrict the implementation of the framework. In the future, the AMR management framework will require precision medicine, artificial intelligence, and One Health-based integration via multidisciplinary collaboration.
    Keywords:  Antimicrobial resistance; ESKAPE pathogens; Non-traditional therapies; One Health
    DOI:  https://doi.org/10.1016/j.micpath.2026.108871
  6. Front Microbiol. 2026 ;17 1954013
      Achromobacter spp. are aerobic, non-fermentative, Gram-negative opportunistic pathogens belonging to the family Alcaligenaceae, order Burkholderiales, and are widely distributed in natural environments such as soil and water. In patients with cystic fibrosis (CF), Achromobacter spp. have emerged as increasingly prevalent opportunistic pathogens, with detection rates in respiratory samples rising from approximately 2-3% in the 1990s and early 2000s to 7-10% by the early 2020s in European and North American registries, although reported rates vary considerably by center, age group, and identification method. These bacteria also affect immunocompromised individuals outside the CF population. However, precise diagnosis and treatment of Achromobacter infections remain particularly challenging because of progressive difficulties: inaccurate species-level identification, limited clinical breakpoints for most species, and synergistic multidrug resistance mechanisms. This review synthesizes recent epidemiological data, outbreak investigations, and tentative epidemiological cutoff values (ECOFFs) for A. xylosoxidans established by EUCAST. We also present an integrated framework that links motility loss, biofilm formation, and resistance development to describe within-host adaptive evolution in the CF airway, and we highlight the role of biofilm-mediated tolerance and persister cells in chronic infection. By synthesizing multidimensional evidence, this review aims to provide a comprehensive reference framework for basic research and clinical management of Achromobacter, and to identify priority research directions, including the establishment of standardized identification procedures and the advancement of standardized clinical development of phage therapy.
    Keywords:  Achromobacter; Achromobacter xylosoxidans; antimicrobial resistance; phage therapy; whole-genome sequencing
    DOI:  https://doi.org/10.3389/fmicb.2026.1954013
  7. Int J Antimicrob Agents. 2026 Oct 07. pii: S0924-8579(26)00319-5. [Epub ahead of print] 108032
       BACKGROUND: The escalating threat of antimicrobial resistance has renewed interest in bacteriophage (phage) therapy, with encapsulation emerging as a promising strategy to enhance phage stability, bioavailability and targeted delivery.
    OBJECTIVES: To comprehensively map and synthesize the available in vivo evidence on encapsulated phage therapy and identify translational gaps relevant to clinical advancement.
    METHODS: Following PRISMA-ScR guidelines, we systematically searched Web of Science Core Collection, Cochrane Central, PubMed, MEDLINE (Ovid), and Scopus.
    RESULTS: Across 56 included studies, research output was concentrated in Asia, particularly India and China. Ionotropic gelation and alginate-based carriers were the most frequently used encapsulation strategies. Oral/gavage administration was the predominant route of phage delivery, with mice and chickens representing the most frequently used animal models. Encapsulated phage demonstrated high encapsulation efficiency, improved survival in simulated gastric fluid, and efficient release in simulated intestinal fluid, with significant therapeutic outcomes reported in 94.6% (53/56) of in vivo studies.
    CONCLUSION: Encapsulated phage therapy shows promising preclinical efficacy, but translational gaps remain. Future research should prioritize large-animal models, long-term studies, and standardized, scalable encapsulation approaches to support clinical translation and regulatory advancement.
    Keywords:  Antimicrobial resistance; Bacteriophage therapy; Encapsulation; in vivo models
    DOI:  https://doi.org/10.1016/j.ijantimicag.2026.108032
  8. Front Microbiol. 2026 ;17 1924276
       Introduction: Enterococcus faecalis is an opportunistic pathogen of One Health relevance and an important reservoir of antimicrobial resistance in poultry production systems. In this study, we generated a large-scale quantitative phage-host interaction dataset to support the rational design of phage cocktails targeting multidrug-resistant poultry-associated E. faecalis.
    Methods: Thirty-eight lytic phages were isolated from poultry farm samples, genomically characterized, and evaluated against 51 clinical poultry isolates using efficiency of plating as a quantitative measure of productive infectivity.
    Results: The complete phage collection achieved 94.12% cumulative strain coverage, while genomic relatedness showed only a moderate association with infectivity profiles, highlighting the need for functional screening. Computational optimization identified a six-phage cocktail, CKT6, which displayed broad in vitro activity against diverse strain backgrounds, reaching 92.16% coverage at MOI 1. Importantly, cocktail performance was not fully predictable from individual phage activity, as host-dependent synergistic and antagonistic effects were observed.
    Discussion: These findings support quantitative phage-host interaction profiling as a robust framework for reproducible and adaptive phage-cocktail design. Further validation under biofilm-associated, formulation-relevant and field-like poultry-production conditions will be required before practical application.
    Keywords:  Enterococcus; antimicrobial resistance; genomic analysis; host range; phage therapy; poultry production
    DOI:  https://doi.org/10.3389/fmicb.2026.1924276
  9. Front Bioeng Biotechnol. 2026 ;14 1963864
      Diabetic foot ulcers (DFUs) have difficulty healing clinically when infection and mature biofilms coexist with hyperglycemic injury, immune dysregulation, oxidative stress, ischemia-hypoxia, repetitive mechanical loading, and extracellular matrix (ECM) degradation. Debridement, infection management, offloading, vascular assessment and revascularization, when indicated, constitute the foundation of care; biomaterials can be evaluated only as adjuncts to this pathway. Hyaluronic acid (HA) is an attractive hydrated ECM-associated and chemically adaptable matrix that can support local retention, controlled release and cell‒material interactions. It is not intrinsically superior to chitosan, alginate, collagen/gelatin or synthetic polymers in every respect: unmodified HA has limited antimicrobial activity and insufficient mechanical strength for many plantar applications. Moreover, antimicrobial, antioxidant, immunomodulatory and angiogenic effects in multicomponent systems are often provided primarily by incorporated antibiotics, metal ions, polyphenols, nitric oxide donors, growth factors or extracellular vesicles rather than by HA itself. This Review therefore distinguishes the contribution of the HA matrix from that of active cargo and separates direct evidence from explicit infected diabetic wound models, indirect evidence from noninfected diabetic wounds, in vitro mechanistic evidence and clinical DFU studies in which infection status was not reported or stratified. Only a minority of preclinical studies have used explicit infected diabetic wound models, and almost all published HA clinical studies have included general populations of DFU patients without biofilm or perfusion stratification. The proposed matching of HA platforms to biofilm-, inflammation/ROS-, ischemia- or ECM-dominant phenotypes is therefore a testable translational hypothesis, not a guideline-endorsed treatment algorithm. Progress requires claim-matched models, full reporting of the HA source, molecular weight distribution, and purification method, endotoxin burden, component deconvolution controls, stage-responsive rather than indiscriminate multifunctionality, long-term local and systemic safety monitoring, and clinical outcomes extending beyond short-term wound closure.
    Keywords:  biofilm; diabetic foot ulcer; hyaluronic acid; hydrogel; infected chronic wound; pathological microenvironment; tissue-engineered biomaterial
    DOI:  https://doi.org/10.3389/fbioe.2026.1963864
  10. Microbiol Res. 2026 Oct 05. pii: S0944-5013(26)00318-6. [Epub ahead of print]314 128754
      Bacteriophages have gained renewed attention as antibacterial agents because they inhibit bacteria through mechanisms distinct from those of antibiotics. However, the practical use of natural phages remains limited by their narrow host range and reduced activity in complex environments. Although phages are abundant in nature, the isolation and screening of phages with properties suited to specific applications can be time-consuming and labor-intensive. Phage engineering offers a means to overcome these limitations by modifying natural phage properties and introducing defined functions. Advances in genetic technologies have enabled the construction of engineered phages with tailored biological activities. Their host specificity and capacity to deliver genetic material also provide a basis for diverse biomedical applications. This review discusses major phage engineering strategies and their applications in bacterial control and detection. These applications include host-range modification, enhancement of antibacterial activity, suppression of bacterial virulence, programmable delivery of genetic payloads, phage-based nanotechnology, and bacterial detection. By integrating engineering strategies with functional applications, this review examines the development of engineered phages from genetic design and functional validation to clinical translation.
    Keywords:  Bacterial control; Bacterial detection; Bacteriophages; Clinical translation; Phage engineering; Synthetic biology
    DOI:  https://doi.org/10.1016/j.micres.2026.128754
  11. J Wound Care. 2026 Oct;35(Sup10C): S1-S24
       BACKGROUND: Diabetic foot ulcers (DFUs) represent a major and growing complication of diabetes in the Gulf and wider Middle East and North Africa (MENA) region, which has the world's highest diabetes prevalence at approximately 17.6% of adults. DFUs carry a high burden of morbidity, mortality and economic cost, and their complex multifactorial aetiology, encompassing peripheral neuropathy, ischaemia, deformity and infection, is compounded by region-specific cultural, climatic and healthcare factors.
    AIMS: To develop evidence-based, Gulf-specific clinical guidelines on the assessment, management and prevention of recurrence of DFUs, applicable across varying levels of healthcare infrastructure and sensitive to the cultural context of the Gulf region.
    METHOD: An international panel of diabetes and wound care experts from the Gulf region and beyond reviewed current international evidence and guidelines and applied it to Gulf-specific practice contexts. Consensus-based recommendations were formulated across the DFU care pathway through a structured expert panel process.
    FINDINGS: The guidelines provide recommendations across five domains: (1) causes and complications, including overlapping aetiological pathways, comorbidities, infection risk, chronicity and psychosocial impact; (2) holistic patient assessment encompassing wound, vascular, neurological, biomechanical, dermatological and footwear evaluation with clear red-flag escalation pathways; (3) management, covering offloading, wound bed preparation, comorbidity optimisation and multidisciplinary collaboration; (4) prevention of recurrence through risk-stratified surveillance, patient education and lifestyle modification; and (5) regional recommendations addressing Gulf-specific clinical, cultural and infrastructural considerations throughout.
    CONCLUSION: Effective management of DFUs in the Gulf and MENA region requires a comprehensive, integrated, multidisciplinary approach grounded in international evidence and calibrated to regional context. These guidelines aim to standardise clinical practice, reduce variation in care and improve outcomes for patients across the region.
    Keywords:  Gulf region; diabetic foot ulcer; multidisciplinary care; peripheral neuropathy; wound offloading
    DOI:  https://doi.org/10.12968/jowc.2026.0559
  12. Int J Low Extrem Wounds. 2026 Oct 09. 15347346261496150
      Diabetic foot ulcers (DFUs) complicated by chronic limb threatening ischemia (CLTI) is one of the most severe pattern of diabetic foot disease (DFD). Although significant improvements in the management of CLTI by the availability of advanced devices and the use of extreme revascularization techniques, there is still a group of patients with unreconstructable vascular disease. These patients have a high risk of major amputation and are commonly defined as no-option CLTI subjects. Nonetheless, by the recent availability of autologous cell therapy (ACT), mainly mononuclear cell therapy, the natural history of no-option CLTI seems to change by a significant improvement in the rate of wound healing and limb salvage. Therefore, authors suggest that the term "no-option CLTI" may no longer be appropriate, as these patients could still have a second chance to achieve limb salvage even after failed revascularization procedures. This editorial highlights the practical implications of ACT for diabetic foot patients with unreconstructable vascular disease, suggesting a new definition and future perspectives.
    Keywords:  autologous cell therapy; diabetic foot; diabetic foot ulcers < lower extremity wound; major amputation; no-option critical limb threatening ischaemia
    DOI:  https://doi.org/10.1177/15347346261496150
  13. bioRxiv. 2026 Aug 13. pii: 2026.08.12.744533. [Epub ahead of print]
      Klebsiella pneumoniae is a WHO critical-priority pathogen for which strain-specific bacteriophages are being explored as precision antimicrobials, yet rapid phage-host matching remains a major barrier to therapeutic deployment. We constructed a comprehensive interaction atlas comprising 84 taxonomically diverse phages and 101 globally sourced, clinically representative K. pneumoniae strains, including multidrug-resistant isolates. Systematic pairwise profiling produced 8,484 interaction measurements, of which 2,656 (31.3%) scored positive for bacterial clearance. Genus was the dominant phage-side determinant of host range, while capsule K-serotype was the strongest host-side determinant of susceptibility; aggregate defense, prophage, plasmid, and antimicrobial-resistance features contributed comparatively little. A genome-guided machine learning model predicted interactions without curated host annotations (AUROC, 0.882; AUPR, 0.765), outperforming a model based only on phage genus and K-serotype and modestly exceeding a curated genomic baseline. The model recovered capsule- and lipopolysaccharide-biosynthesis genes, canonical receptors and defense-associated features as major predictors using SHAP analysis. Feasibility tests of expert- and model-selected cocktails exposed a translational constraint. Although all formulations suppressed growth in vitro , only the specific cocktail whose phages replicated robustly within the murine gut reduced colonization, suggesting in vivo amplification rather than predicted host range as the limiting factor for therapeutic efficacy. Together with the activity of a model-selected cocktail built for an isolate completely excluded from training, these results provide a species-wide resource for K. pneumoniae phage matching and support a hybrid workflow combining genome-based ranking with targeted phenotypic validation.
    DOI:  https://doi.org/10.64898/2026.08.12.744533
  14. Water Res. 2026 Sep 28. pii: S0043-1354(26)01703-3. [Epub ahead of print]308(Pt C): 127032
      Antimicrobial resistance (AMR) poses a serious threat to global public health, with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species - collectively known as ESKAPE pathogens - as high priority threats. Bacteriophages represent a potential alternative therapy for AMR infections. While many of the bacteriophages that target ESKAPE pathogens have been isolated from environmental sources, such as wastewater, the global distribution of these bacteriophages remains poorly understood. In this study, metagenomic sequencing of wastewater was used to assess the presence and distribution of known bacteriophages in urban wastewater collected from 62 sites worldwide. Focusing specifically on lytic bacteriophages known to target ESKAPE pathogens, a literature review was conducted to curate a collection of bacteriophages with known therapeutic properties and publicly available genomes. The presence and distribution of these therapeutic bacteriophages in wastewater were examined, both geographically and temporally. Our analysis revealed a high abundance of bacteriophage families associated with the human gastrointestinal tract, as well as those infecting bacteria native to aquatic environments. Bacteriophages similar to those targeting ESKAPE pathogens were detected across the wastewater samples, except for bacteriophages targeting Staphylococcus aureus. Both the presence and abundance of these putative ESKAPE-phages varied considerably across regions, with African sample sites exhibiting the highest diversity and European sample sites the lowest. No clear temporal trends were observed for these bacteriophages. This study provides the use of wastewater to provide insights into the global diversity and distribution of bacteriophages, with a specific focus on species with therapeutic potential against ESKAPE pathogens, while further offering a valuable dataset for future bacteriophage research.
    Keywords:  ESKAPE pathogens; Global wastewater; Metagenomic sequencing; Therapeutic bacteriophages
    DOI:  https://doi.org/10.1016/j.watres.2026.127032
  15. Int J Nanomedicine. 2026 ;21 650676
      Pulpitis (Pul) and periodontitis (PD) are oral infectious diseases with extremely high global prevalence. These pathologies can induce severe pain, significantly elevate the risk of tooth mobility and eventual tooth loss, and have been confirmed to be closely correlated with multiple chronic systemic disorders including diabetes mellitus and cardiovascular diseases. Conventional clinical interventions for these diseases are frequently characterized by incomplete debridement and inefficient drug delivery. Additionally, the growing threat of antimicrobial resistance presents an ongoing challenge for traditional treatments, leading to overall unsatisfactory therapeutic outcomes. Nanomaterials offer an innovative approach to overcoming the aforementioned limitations of conventional treatments, owing to their distinctive physicochemical properties, intrinsic antibacterial, anti-inflammatory and antioxidant activities, as well as their ability to facilitate bone and cementum regeneration. However, the development of nanotherapeutics for Pul and PD currently remains inefficient. Most existing nanomaterial systems exhibit poor adaptability to the complex oral microenvironment, and are unable to achieve closed-loop dynamic regulation during the entire therapeutic process. The rapid development of artificial intelligence (AI) has brought unprecedented new opportunities to resolve these bottlenecks. By enabling an intelligent "sense-analyze-respond" feedback loop, AI can optimize the key performance parameters of nanomaterials and facilitate dynamic adjustment of clinical therapeutic regimens. This review firstly sorts out the pathogenesis of Pul and PD, as well as the corresponding targeted intervention strategies enabled by nanomaterials. Subsequently, the existing nanomaterial systems are categorized based on their dimensional classification (0D to 3D), and their therapeutic applications and current limitations in the treatment of both diseases are analyzed. Finally, this paper discusses the research prospects of AI-enabled nanomaterials in structural design and in the management of Pul and PD. This review aims to provide theoretical reference for the development of more precise and effective therapeutic strategies for these two prevalent oral diseases.
    Keywords:  artificial intelligence; nanomaterials; oral infection; periodontitis; pulpitis
    DOI:  https://doi.org/10.2147/IJN.S650676
  16. Health Sci Rep. 2026 Oct;9(10): e73353
       Background and Aims: Wound care is a critical component of postoperative and chronic disease management, yet rising supply costs, inconsistent insurance coverage, and patient-level barriers can complicate care in outpatient and home settings. This narrative review summarizes wound-management principles and evaluates lower-cost alternatives, emphasizing differences in evidence strength, appropriate wound contact, contraindications, and required clinical oversight.
    Methods: A narrative review of English-language literature available through July 2026 was conducted using PubMed/MEDLINE, Google Scholar, Scopus, Web of Science, and reference-list review. Evidence from guidelines, systematic reviews, meta-analyses, randomized trials, and clinical studies was prioritized. Evidence supporting each lower-cost strategy was categorized qualitatively by study design and directness.
    Results: Evidence was strongest for potable tap-water cleansing in selected wounds, plain petrolatum for selected clean postprocedural wounds, and paper tape for selected closed incisions. Nonmedical absorbent products have a limited role as external secondary protection and should not contact open wound beds. Clinician-assembled negative-pressure wound therapy and nonmedical compression require trained selection and monitoring. Raw honey, direct application of essential oils, and unsupervised homemade wound solutions are not recommended.
    Conclusion: Certain lower-cost wound care products may expand access to care for patients facing financial or logistical barriers. However, these alternative products should preserve the same safety threshold as conventional care and should be selected according to wound type, depth, exudate, perfusion, infection status, and treatment goal. Further comparative research is needed to establish the effectiveness, safety, and cost savings of alternative wound care strategies.
    Keywords:  education; health equity; lower‐cost care; wound; wound care; wound dressing
    DOI:  https://doi.org/10.1002/hsr2.73353
  17. Braz J Microbiol. 2026 Oct 09. pii: 289. [Epub ahead of print]57(1):
      Pathogenic Escherichia coli biofilms pose a significant challenge in veterinary and clinical settings due to their high antibiotic resistance. This study characterizes the E. coli bacteriophage vB_EcoS_MS2 as a potential targeted biocontrol agent against these pathogens. Host range determination revealed high specificity, with vB_EcoS_MS2 lysing only select E. coli strains and demonstrating superior replication efficiency (Efficiency of Plating: 112.57%) on strain C4 compared to its propagation host, MS2. While nutrient limitation strongly induced biofilm formation in in vitro assays, phage vB_EcoS_MS2 demonstrated potent prophylactic activity, inhibiting initial biofilm development by over 70% across all tested concentrations (10⁴-10⁹ PFU/mL). Conversely, the phage showed limited and transient efficacy in eradicating mature, 48-hour-old biofilms under the tested conditions. Whole-genome sequencing confirmed a 40,209 bp circular genome belonging to the class Caudoviricetes, encoding a robust holin-endopeptidase lytic cassette without carrying known antimicrobial resistance determinants. These findings indicate that while vB_EcoS_MS2 is highly effective for prophylactic biofilm prevention, complementary strategies may be required to clear established biofilms.
    Keywords:   Caudoviricetes ; Escherichia coli ; Biocontrol; Biofilm prophylaxis; Phage therapy; Whole-genome sequencing
    DOI:  https://doi.org/10.1007/s42770-026-02116-2
  18. Cell Rep Med. 2026 Oct 09. pii: S2666-3791(26)00524-0. [Epub ahead of print] 103107
      The early-life assembly of the gut microbiome is a critical determinant of long-term health, yet the role of bacteriophages in this process remains poorly understood. Here we longitudinally profile the gut phageome of 34 mother-infant dyads during the first year of life with metagenomics and a phage-centered computational workflow. Phage diversity increases with age, paralleling bacterial diversification but following distinct ecological trajectories. Shared viral populations across maternal and infant samples are consistent with potential maternal contribution, although not indicative of direct transmission. Feeding-related variables are consistently associated with phageome composition at specific developmental stages. No single factor fully explains phageome variation, supporting a multifactorial model involving maternal, environmental, and dietary inputs. Together, these findings provide a framework for understanding early-life phage ecology, positioning phages as active participants in early microbiome assembly and supporting the inclusion of viral components in microbiome-based strategies aimed at promoting healthy ecosystem development in infancy.
    Keywords:  Bifidobacterium; bacteriophages (phages); breastfeeding; early life; infant gut; maternal-infant sharing; metagenomics; phage ecology
    DOI:  https://doi.org/10.1016/j.xcrm.2026.103107
  19. J Appl Microbiol. 2026 Oct 05. pii: lxag248. [Epub ahead of print]
      As interest continues in bacteriophages as precision antimicrobials, understanding the molecular determinants of host range has become more important. Here, we use the term polyvalent to describe phages whose broad host recognition is associated with more than one receptor-binding protein (RBP) and/or more than one experimentally supported receptor-recognition pathway, which is distinct from broad host range as a phenotypic description alone. We propose a stochastic-cooperative hypothesis in which some RBPs can contribute primarily to reversible surface encounter and retention, whereas other RBPs mediate the stable receptor binding required to progress toward genome delivery. The novelty of this hypothesis is not the established reversible-to-irreversible sequence of adsorption, nor the existence of phages with multiple RBPs, but the specific prediction that functionally non-equivalent RBPs can alter the probability distribution of transitions between adsorption states on heterogeneous bacterial surfaces. Available structural, genetic, and single-particle evidence is consistent with parts of this interpretation but does not currently demonstrate a universal auxiliary-first pathway. Therefore, we distinguish evidence-supported elements from hypothetical components, consider alternative explanations for broad host range, and define experimentally testable predictions at molecular, single-particle, cellular, and population scales. This Perspective is intended as an experimentally evaluable conceptual model for studying how receptor density, accessibility, RBP composition, and post-adsorption barriers jointly shape observed host range, rather than as an established mechanism for all polyvalent phages.
    Keywords:  Polyvalent phages; bacterial receptors; host range; phage engineering; receptor-binding proteins; stochastic-cooperative adsorption
    DOI:  https://doi.org/10.1093/jambio/lxag248
  20. Front Oral Health. 2026 ;7 1926663
      Periodontitis is a common chronic inflammatory disease, and oral health problems are frequent in people with Parkinson's disease (PD). Observational studies consistently indicate poorer periodontal status in PD, but evidence that periodontitis increases the incidence or progression of PD is inconsistent and does not establish causality. This narrative review summarizes current evidence on epidemiological associations, biologically plausible mechanisms, and dental management considerations. Human data support an association between PD and greater periodontal disease burden, plausibly related to motor impairment, reduced self-care capacity, salivary dysfunction, and altered oral microbial ecology. By contrast, proposed pathways from periodontitis to PD, including systemic inflammation, blood-brain barrier disruption, microbial products, and the oral-gut-brain axis, are supported mainly by preclinical, indirect, or low-level human evidence and should be regarded as hypotheses rather than established mechanisms. Observational reports of lower PD incidence among individuals receiving dental scaling do not demonstrate a preventive effect of periodontal treatment. In clinical practice, periodontal care should therefore be justified by established oral-health needs and individualized for PD-related motor, swallowing, cognitive, medication, and device-related considerations, rather than presented as a strategy to prevent or modify PD. Better longitudinal studies and interventional trials are needed to clarify temporality, mechanisms, and any neurological effects of periodontal treatment.
    Keywords:  Parkinson's disease; dysbiosis; neuroinflammation; oral health management; oral microbiome; periodontitis
    DOI:  https://doi.org/10.3389/froh.2026.1926663
  21. Vet Res Commun. 2026 Oct 09. pii: 625. [Epub ahead of print]50(6):
      Phages show promising application prospects as antibacterial agents for the treatment of drug-resistant bacterial infections. However, the rapid evolution of phage resistance in bacteria has compromised the therapeutic efficacy. Here, we first screened a broad-host-range phage PC13 based on the Salmonella-phage library. Then, phage-resistant Salmonella mutants were obtained by serial co-culture passages of PC13 Salmonella enterica subsp. enterica serovar Enteritidis C2. Whole-genome sequencing analyses were performed on the phages and resistant strains to decipher the potential molecular mechanisms of phage-host interactions and collateral sensitivity. The bacteriostatic and therapeutic effects of the triple phage cocktail (PC13 + PC11+PC16) against S. Enteritidis C2 were evaluated using in vitro bacteriostatic assays and in vivo chicken infection models. The results showed that PC13 lysed 90% (81/90) of the tested chicken-derived Salmonella isolates. PC11 achieved a lysis rate of 95% against all 20 PC13-resistant mutants. Relative to single-phage PC13 and the PC13 + PC11 cocktail, the triple-phage cocktail PC13 + PC11 + PC16 markedly extended bacteriostatic time in vitro (p < 0.01). The phage cocktail significantly prolonged the bacteriostatic time in vitro compared to individual phages (p < 0.01). Comparative genomic analysis revealed that 95% of the PC13-resistant mutants harbored missense, nonsense, or frameshift mutations in genes associated with lipopolysaccharide (LPS) core oligosaccharide synthesis. These PC13-resistant mutants exhibited significantly enhanced susceptibility to PC11 and PC16 relative to the wild-type strain (p < 0.05). We propose that Salmonella evaded PC13 infection by altering LPS structure via these mutations, and these genetic changes simultaneously exposed the putative binding receptors predicted for PC11 and PC16, conferring collateral sensitivity of the resistant mutants to the latter two phages. In the chicken S. Enteritidis infection model, compared with the Salmonella treatment group, the fecal Salmonella load of chicks in the cocktail treatment group decreased by about 4.0 log CFU/g, and there was no significant difference in body weight changes compared with control group. In conclusion, a phage cocktail against S. Enteritidis with significantly enhanced antibacterial activity was rationally formulated constructed by targeting phage-resistant escape mutants generated during phage-bacterial coevolution. The collateral sensitivity effect uncovered in this study explains its superior inhibitory performance, which provides theoretical and practical strategies for developing highly efficient phage therapy.
    Keywords:   Salmonella Enteritidis; Collateral sensitivity; Drug-resistant bacteria control; Phage cocktails; Phage-host coevolution
    DOI:  https://doi.org/10.1007/s11259-026-11519-3
  22. Cell Host Microbe. 2026 Oct 08. pii: S1931-3128(26)00398-7. [Epub ahead of print]
      Bacteriophages drive pathogen evolution, yet the mechanisms governing phage susceptibility in native bacterial backgrounds, and their consequences within mammalian hosts, remain poorly understood. Here, we mapped >1,000 interactions between 20 diverse Salmonella isolates and 52 wild phages from global disease reservoirs, integrating genome-scale fitness profiling with comparative genomics. Receptor identity and surface phase variation, including Hin-mediated flagellar switching, explained ∼67% of phage susceptibility patterns, identifying cell-surface architecture as the major determinant of phage host range in Salmonella. Among resistance phenotypes not explained by surface features, we discovered anti-phage-packaging agent (AppA), a prophage-encoded defense factor that abrogates phage replication within its native host. AppA inhibits phage DNA packaging through functional mimicry of a terminase assembly interface, revealing a previously unrecognized mechanism of phage defense. AppA is expressed under conditions encountered during mammalian infection and suppresses phage expansion in the murine gut, demonstrating that prophage-encoded single-gene defenses can shape disease outcomes in vivo.
    Keywords:  Rb-Tn-seq; Salmonella; anti-phage; bacteriophage; defense; genetics; host-pathogen; mouse model; native; pathogen; phase variation; prophage; receptor; systems biology; tropical diseases
    DOI:  https://doi.org/10.1016/j.chom.2026.09.009
  23. Curr Microbiol. 2026 Oct 08. pii: 589. [Epub ahead of print]83(11):
      The increase of antimicrobial resistance (AMR), particularly among the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. poses a critical global threat to public health by severely limiting effective therapeutic options. These pathogens employ diverse and efficient survival strategies, including drug-degrading enzymes, target modification, porin loss, efflux pump overexpression, and biofilm formation, leading to multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-resistant clinical phenotypes. As conventional antibiotic discovery slows and treatment failures rise, natural products have re-emerged as a promising source of chemically diverse leads with antibacterial activity. Plants and microbes biosynthesize structurally diverse secondary metabolites such as polyketides, alkaloids, flavonoids, phenolics, terpenoids, and saponins, many of which exhibit broad-spectrum antibacterial activity and synergize with existing antibiotics while exerting reduced selective pressure for resistance. Several compounds demonstrated potent antibacterial activity with MIC values ranging from 0.1 to 32 µg/mL, highlighting their therapeutic potential. This review provides a comprehensive analysis of natural product-based strategies against ESKAPE pathogens, highlighting their mechanisms of action: membrane disruption, inhibition of efflux pumps, interference with DNA/protein synthesis, suppression of quorum sensing, and inhibition of biofilm formation. Special emphasis is placed on alkaloids, flavonoids, and terpenoids whose antibacterial potential is closely linked to defined structure-activity relationships (SAR). Alkaloids such as berberine, sanguinarine, and conessine show potent activity by targeting cell wall integrity, FtsZ-mediated division, and efflux systems, while specific flavonoid subclasses exhibited enhanced antibacterial potency through key structural features such as 5,7-dihydroxylation, prenylation, and optimized B-ring substitutions. Numerous natural products discussed demonstrate clinically relevant activity against MDR S. aureus, carbapenem-resistant K. pneumoniae, A. baumannii, and P. aeruginosa, supporting their potential as lead compounds or adjuvant agents.
    DOI:  https://doi.org/10.1007/s00284-026-05166-9
  24. Diabetes Res Clin Pract. 2026 Oct 08. pii: S0168-8227(26)00524-3. [Epub ahead of print] 113604
      Delayed healing of diabetic foot ulcers (DFUs) remains a clinical challenge, and the relationships among glycemic control, wound healing progression, and morphological characteristics in DFUs remain systematically unmapped. This scoping review synthesized current evidence on these relationships. Following PRISMA-ScR guidelines, PubMed, Scopus, MEDLINE, and CINAHL were searched on April 2026. Eligible studies included adults with DFUs reporting glycemic parameters alongside wound morphology or healing progression. Twenty-two studies were included. HbA1c was the most frequently evaluated glycemic parameter, followed by fasting and postprandial glucose. Poorer glycemic control was associated with less favorable healing outcomes in several studies, including delayed healing, reduced healing velocity, treatment failure, and amputation; however, the direction and strength of these associations varied across studies. Direct evidence linking glycemic parameters to specific wound morphological characteristics was limited and heterogeneous, with reported associations involving wound size and depth, while other studies found no significant associations. Dynamic glycemic monitoring was rarely assessed, with glycemic variability evaluated in only one study. Current evidence does not establish a unidirectional causal relationship between glycemic control and wound morphological changes or specific glycemic targets for individual healing progression. Prospective longitudinal studies integrating repeated dynamic glycemic monitoring with standardized serial wound morphology assessment are needed.
    Keywords:  Diabetic ulcer; Glucose monitoring; Glycemic control; Hyperglycemia; Wound healing
    DOI:  https://doi.org/10.1016/j.diabres.2026.113604
  25. J Tissue Viability. 2026 Sep 30. pii: S0965-206X(26)00078-1. [Epub ahead of print]35(4): 101060
       BACKGROUND: Chronic non-healing wounds are associated with substantial morbidity, mortality, and healthcare costs. Copper has attracted sustained attention because it combines pro-healing, pro-angiogenic, and antibacterial activities. However, the temporal evolution of this field and the transition from mechanistic studies to advanced copper-containing wound dressings have not been systematically visualized. This study aimed to map the research landscape, identify major hotspots, and characterize emerging directions in copper-based wound-healing research from 2000 to 2025.
    METHODS: Publications published between 2000 and 2025 were retrieved from the Web of Science Core Collection. CiteSpace was used to perform country, institution, author, journal, keyword co-occurrence, keyword-clustering, and burst-keyword analyses to visualize the intellectual structure and temporal development of the field.
    RESULTS: A total of 625 publications, comprising articles and review articles, were included. China was the leading contributor by publication output, and the Chinese Academy of Sciences was among the most productive institutions. The International Journal of Biological Macromolecules was the most productive journal in the dataset. Frequently occurring keywords included "Wound Healing," "Nanoparticles," and "Antibacterial." Keyword-clustering and burst analyses suggested a thematic progression from biological and molecular topics, including morphogenesis, expression, activation, and angiogenesis, toward copper nanoparticles, drug delivery, antibacterial therapy, green synthesis, hydrogels, metal-organic frameworks, and nanofibers.
    CONCLUSION: The bibliometric evidence suggests three overlapping thematic phases in copper-related wound-healing research: biological and mechanistic exploration, nanomaterial design and sustainable preparation, and multifunctional therapy using advanced wound-dressing platforms. Recent research themes emphasize controlled copper-ion release, antibacterial activity, cytocompatibility, and the integration of copper with hydrogels, nanofibers, metal-organic frameworks, and other biomaterials. These findings provide a bibliometric framework for future studies aimed at improving the safety, reproducibility, and translational potential of copper-based wound therapies.
    Keywords:  Antibacterial therapy; Bibliometric analysis; CiteSpace; Copper; Copper nanoparticles; Hydrogels; Nanofibers; Wound healing
    DOI:  https://doi.org/10.1016/j.jtv.2026.101060
  26. Front Pharmacol. 2026 ;17 1915973
       Background: Artificial intelligence (AI)-assisted drug repurposing seeks to identify new therapeutic applications for existing drugs. Nevertheless, most of the existing studies are centered on prediction scores and candidate ranking, and there is still relatively little attention paid to the pharmacological mechanisms, safety and translational validation.
    Objective: This critical review summarizes existing AI approaches to drug repurposing, identifies their mechanistic, safety, and translational barriers, and incorporates the emerging evidence gaps into a mechanism-driven and safety-proven translational pharmacology model.
    Findings: The literature reviewed shows that machine learning, deep learning, network medicine, knowledge graphs, graph neural networks, and foundation models have the potential to significantly increase the number of candidates identified, but they have marked variations in terms of interpretability, biological support, safety integration, external validation, and clinical applicability. In all of these strategies, common shortcomings are inadequate mechanism validation, poor causal evidence, incomplete dose and safety evaluation, weak pharmacovigilance integration, and reliance on internal validation, and varying experimental or real-world confirmatory evidence. These persistent evidence gaps were incorporated into a sequence of steps that incorporates candidate predictions, mechanism mapping, determination of causal plausibility, safety and toxicity evaluation, pharmacovigilance, real-world validation, expert pharmacology review and evidence-based candidate prioritization.
    Conclusion: AI-driven drug repurposing presents huge potential in the field of therapeutic innovation, but current applications require more clinical evidence and pharmacological mechanisms demonstrating safety, as well as clinical relevance. The proposed framework can support the more reliable prioritization of candidates for experimental testing, real world validation and future clinical testing.
    Keywords:  artificial intelligence; drug repurposing; mechanism-aware AI; pharmacovigilance; safety validation; translational pharmacology
    DOI:  https://doi.org/10.3389/fphar.2026.1915973
  27. Front Cell Infect Microbiol. 2026 ;16 1891369
       Background: Echinocandins have emerged as potential therapeutic options for urinary tract infections (UTIs), particularly involving multidrug-resistant fungi. Given the fragmented nature of the evidence and the lack of comprehensive synthesis, this study aimed to systematically evaluate the global research landscape, collaboration networks, and emerging hotspots in this field through a bibliometric analysis.
    Methods: Publications related to echinocandin therapy for UTIs from database inception to March 20, 2026 were retrieved from PubMed and Web of Science. This bibliometric review was conducted and reported in accordance with the BIBLIO (Preliminary Guideline for Reporting Bibliometric Reviews of the Biomedical Literature) minimum requirements. VOSviewer (1.6.20) was used for collaboration network and keyword co-occurrence analysis. CiteSpace (6.4.R1) was used for burst detection, timeline visualization, and cluster analysis. Additional bibliometric indicators including total citations, average citations per publication, H-index, citation density, and identification of influential journals were calculated.
    Results: A total of 47 publications were included, with peaks in 2016 and 2025 (six each). The limited number of publications reflects the emerging nature of this research field and the ongoing debate regarding the role of echinocandins in UTI management. The United States and Spain were leading contributors. Keyword analysis revealed a shift from early themes toward multidrug-resistant pathogens, particularly Candida auris, Candida glabrata, and multidrug resistance. Cluster analysis identified eight significant clusters Q = 0.755, S = 0.9196, focusing on candidate drugs, pathogen identification, and antifungal resistance mechanisms.
    Conclusion: Research on echinocandins for UTIs remains limited but shows sustained interest. The field has evolved toward multidrug-resistant fungal pathogens. Lack of robust clinical evidence remains a major barrier. Future studies should prioritize prospective clinical investigations and pharmacokinetic/pharmacodynamic evaluations.Robust prospective clinical studies and PK/PD evaluations remain essential to establish definitive therapeutic role. We advocate for updated, evidence-based stewardship protocols that clearly define indications for echinocandin use in fluconazole-refractory UTIs.
    Keywords:  Citespace; VOSviewer; antifungal resistance; bibliometric analysis; candiduria; echinocandins; urinary tract infection
    DOI:  https://doi.org/10.3389/fcimb.2026.1891369
  28. Infect Immun. 2026 Oct 07. e0043526
      The development of predictive understanding of bacterial resistance to antibiotics is one of the greatest challenges of modern medicine. Genome-scale metabolic models (GEMs) are mathematical representations of the metabolic network of a given organism assembled from genomic data that predict cellular activity across many environmental and genetic contexts. Because a single model can be solved under thousands of conditions, GEMs generate data at scales that support downstream analysis with artificial intelligence tools, helping to elucidate how pathogens adapt to host environments, evade immune responses, and acquire resistance. Here, we review how GEMs of ESKAPE pathogens are built, what data they require, and what they can and cannot do. We describe the reconstruction workflow from automated draft network through manual curation, gap filling, and experimental validation and the public and experimental data sources each stage depends on. We then describe how accessory genes and transcriptomic measurements are incorporated to yield strain- and condition-specific models and where machine learning contributes both in expanding functional annotation and in consuming model-generated flux distributions. Applications are illustrated with ESKAPE examples throughout, including conserved metabolic vulnerabilities identified across strain collections and flux rewiring observed under antibiotic exposure. Despite this progress, high-quality GEMs exist for only a fraction of ESKAPE species; many are constrained by incomplete annotation or limited experimental validation, and non-metabolic resistance mechanisms are captured only insofar as they impose a metabolic cost. Providing reliable tools to build new models from trustworthy templates, therefore, remains a priority for narrowing the gap between genotype and phenotype.
    Keywords:  ESKAPE pathogens; computational biology; flux-to-AI; genome-scale metabolic modeling
    DOI:  https://doi.org/10.1128/iai.00435-26
  29. Microb Pathog. 2026 Oct 07. pii: S0882-4010(26)00595-4. [Epub ahead of print]221 108869
      Apical periodontitis poses a significant challenge, as 80% of cases are linked to Enterococcus faecalis, which is often protected within a biofilm. Phage-antibiotic synergy (PAS) presents a promising approach to overcoming resistance, though evidence from disease-relevant models, particularly in vivo, remains limited. In this study, we demonstrate that the lytic phage PEf771, when combined with either amoxicillin or ampicillin trihydrate, effectively eliminates multidrug-resistant E. faecalis YN771 across various contexts, including planktonic cultures, mature biofilms, ex vivo infected teeth, and in rat models of peritoneal and apical periodontitis infection. Co-treatment reduced planktonic viable counts by up to 5.4 log10 CFU/mL within 12 h and removed 62-68% of preformed biofilm within 4 h. The combination also converted the transient transcriptional repression achieved by phage alone into durable silencing of the biofilm determinants ebpC, gelE, and esp, which remained 68-81% below control levels. In vivo, the regimens preserved animal survival, limited organ damage, and enriched commensal taxa including Akkermansia muciniphila and Ruminococcaceae UCG-014, while histological analysis revealed reduced periapical inflammation and early periodontal-ligament repair. These findings establish PAS as an immediately translatable, resistance-sparing adjunct for refractory endodontic infections and provide a framework for pairing phages with front-line β-lactams against recalcitrant biofilm diseases.
    Keywords:  Apical periodontitis; Biofilm; Eradication; Gut microbiota; Phage; Synergy
    DOI:  https://doi.org/10.1016/j.micpath.2026.108869
  30. One Health. 2026 Dec;23 101573
      Antimicrobial resistance (AMR) poses a critical global health challenge, leading to substantial mortality and economic losses without science-based interventions. Conventional approaches to combating AMR have important limitations in addressing this escalating threat. Recent advances in AI, including deep learning, large language models, and protein language models, provide new opportunities to integrate multimodal data for AMR research. However, evidence remains uneven, with many approaches limited to computational benchmarking rather than real-world validation. Here, we critically review AI applications in AMR, focusing on rapid diagnosis, therapeutic discovery, and clinical decision support. AI-based diagnostic models can identify resistant pathogens and predict resistance profiles, but most lack prospective clinical evaluation. AI-assisted drug discovery and alternative therapies have generated promising candidates, although most remain at computational, in vitro, or early preclinical stages. Large language models may support decision-making, but their clinical use remains preliminary. Successful translation of AI into clinical and One Health practice will require representative datasets, independent validation, prospective evaluation, and robust governance.
    Keywords:  Antimicrobial resistance; Artificial intelligence; Drug discovery; Large language model; Machine learning; One Health
    DOI:  https://doi.org/10.1016/j.onehlt.2026.101573
  31. Front Endocrinol (Lausanne). 2026 ;17 1925839
       Background: This study aimed to comprehensively evaluate the association of twelve inflammation-related biomarkers with amputation level (major vs. minor) in diabetic foot ulcer (DFU) patients undergoing amputation, with particular focus on identifying the strongest associated factor and exploring differences between above-knee amputation (AKA) and below-knee amputation (BKA).
    Methods: We retrospectively enrolled DFU patients who underwent amputation between January 2020 and June 2025. Twelve indices were calculated: SIRI, SII, AISI, NAR, MAR, RAR, HALP, PNI, ALI, CALLY, IBI, and CLR. LASSO regression and multivariate logistic regression were used for variable selection. AUC comparisons and Bootstrap internal validation assessed model performance. Subgroup analysis compared AKA vs. BKA.
    Results: A total of 538 patients were included (271 major, 267 minor). In univariate analysis, higher levels of NAR, MAR, RAR, SIRI, SII, AISI, IBI, and CLR were associated with major amputation, whereas lower levels of HALP, PNI, ALI, and CALLY were associated with major amputation. RAR exhibited the highest odds ratio (OR = 3.25, 95% CI: 2.54-4.16, p < 0.001) for major versus minor amputation. LASSO regression selected eight indices; multivariate analysis confirmed RAR, HALP, PNI, and ALI as independently associated with amputation level. The combined model incorporating RAR, HALP, PNI, and ALI demonstrated superior predictive performance compared to RAR alone (AUC: 0.816 vs. 0.773, p = 0.001). Bootstrap validation confirmed the stability of the combined model (optimism-corrected AUC: 0.811; optimism: 0.005). In the exploratory subgroup analysis, AKA patients had significantly higher RAR levels and lower PNI and ALI levels compared to BKA patients (all p < 0.05); however, only RAR remained significantly associated with AKA after multivariable adjustment.
    Conclusion: The combined model may provide modest incremental predictive value over RAR alone, but the clinical gain is limited. RAR alone remains a practical and sufficient tool for risk stratification, particularly in resource-limited settings. However, these findings are retrospective, and external validation is warranted before clinical application.
    Keywords:  LASSO regression; RAR; above-knee amputation; below-knee amputation; diabetic foot ulcer; inflammation-related biomarkers; major amputation
    DOI:  https://doi.org/10.3389/fendo.2026.1925839
  32. Spec Care Dentist. 2026 Sep-Oct;46(5):46(5): e70272
       AIMS: To evaluate the available evidence on the association between oral microbiota composition and Parkinson's disease (PD), including its relationship with disease severity and clinical features.
    METHODS AND RESULTS: This systematic review was registered in PROSPERO (CRD42024560059) and conducted according to the PRISMA 2020 statement. Searches were performed in PubMed, Embase, Web of Science, LILACS, Scopus, and SciELO. Observational studies evaluating the oral microbiota of adults with PD were included. Eleven studies, predominantly case-control, were analyzed, with 16S rRNA sequencing used in 90.9% of them. The genera most frequently associated with PD were Lactobacillus (45.45%), Prevotella (36.7%), and Streptococcus (36.7%). Most studies reported differences in beta diversity, indicating a distinct oral microbial profile in patients with PD. Higher Lactobacillus abundance and lower Neisseria abundance were associated with greater disease severity and poorer cognitive performance in some studies. According to the GRADE approach, the certainty of the evidence was very low.
    CONCLUSION: The available evidence suggests that PD is associated with alterations in oral microbiota composition. However, because the evidence is derived predominantly from observational studies, causal relationships cannot be established. Longitudinal studies using standardized microbiome methodologies are needed to validate these microbial signatures as candidate biomarkers.
    Keywords:  Parkinson's disease; biomarkers; chronic disease; dysbiosis; microbiota; neurobehavioral manifestations; oral cavity
    DOI:  https://doi.org/10.1111/scd.70272
  33. Eur Respir Rev. 2026 Oct;pii: 250282. [Epub ahead of print]35(182):
      While culturing the opportunistic pathogen Pseudomonas aeruginosa in standard bacterial culture media has provided fundamental insights into its pathological properties such as virulence and antibiotic resistance, growing evidence suggests that these conditions fail to accurately reflect the in vivo bacterial physiology. In the lungs of people living with cystic fibrosis (pwCF), where P. aeruginosa is a major contributor to the disease process, bacteria reside within a complex physicochemical environment that drives their behaviour. Until recently, efforts to evaluate how well laboratory models mimic these in vivo conditions were hampered by limited data on the physiology of P. aeruginosa during chronic cystic fibrosis (CF) lung infections. However, several omics-based studies have now successfully characterised P. aeruginosa from human CF sputum, revealing unique adaptation patterns associated within this niche. This data enables evaluating the physiological relevance of in vitro and in vivo model systems, hereby highlighting the usefulness (and limitations) of models that mimic aspects of the physicochemical in vivo environment for studying P. aeruginosa infections in CF. In this review, we summarise a range of models of P. aeruginosa infection, including artificial sputum medium, air-liquid interface cell culture, ex vivo pig lung and mouse models, that have been evaluated for their physiological resemblance using omics-based approaches. We also address the current lack of proteomic and metabolomic validation approaches and outline key considerations and future directions to guide the continued refinement of experimental model systems.
    DOI:  https://doi.org/10.1183/16000617.0282-2025
  34. Infect Dis Ther. 2026 Oct 06.
       INTRODUCTION: Diabetic foot infections (DFIs), frequently complicated by acute osteomyelitis (AOM), are associated with substantial morbidity and are increasingly difficult to manage due to antimicrobial resistance and treatment-related toxicities. Omadacycline is a broad-spectrum aminomethylcycline with favorable safety characteristics and oral bioavailability, but real-world data in DFI and AOM are limited.
    METHODS: We conducted a prospective, open-label, two-center study evaluating omadacycline for hospitalized adults with moderate-to-severe DFI with or without AOM who were at high risk for adverse events from standard therapy. Outcomes were compared with a 2:1 matched historical cohort treated with standard of care. The primary endpoint was clinical success at end of therapy (EOT); secondary endpoints included clinical success at test-of-cure (TOC), safety outcomes, and healthcare utilization.
    RESULTS: A TOTAL OF 14 patients received omadacycline and were matched to 28 historical controls. AOM was present in 64.3% of patients in both groups, while systemic inflammatory response syndrome was more common in the omadacycline group. Clinical success at EOT was achieved in 90% of omadacycline-treated patients versus 85.7% of controls (p = 0.999). TOC success rates were similar (60% vs. 64.3%, p = 0.999). All omadacycline patients transitioned to oral therapy and none required central venous catheter placement, compared with 71.4% of controls (p < 0.001). Serious adverse drug events occurred in no omadacycline patients versus 25% of controls.
    CONCLUSIONS: In this real-world analysis, there was no observed difference in efficacy between omadacycline and standard care for DFI, including cases complicated by AOM, with few adverse events observed. These findings support continued evaluation and potential use of omadacycline in treating select patients with DFIs.
    TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04714411.
    Keywords:  Antimicrobial stewardship; Diabetic foot infection; Omadacycline; Osteomyelitis; Real-world evidence
    DOI:  https://doi.org/10.1007/s40121-026-01450-0
  35. Microbiol Spectr. 2026 Oct 06. e0165226
      Treatment of healthcare-associated infections is becoming increasingly challenging due to rising antimicrobial resistance (AMR). As clinical microbiology and public health continue to transition toward whole-genome sequencing (WGS) for outbreak detection, diagnostics, and surveillance, the ability to accurately predict antimicrobial resistance from genomic sequence data will become crucial. In this study, in silico antimicrobial resistance prediction with the Staramr tool was refined from whole-genome sequencing data for four top-priority healthcare-associated bacteria: carbapenemase-producing Escherichia coli, carbapenemase-producing Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. Isolates (n = 4,876) were collected in Canada within two national surveillance programs: the Canadian Nosocomial Infection Surveillance Program and the Canadian Ward Study. Broth microdilution was used as the gold standard to evaluate the performance of Staramr. The average sensitivity, specificity, and concordance of categorical antimicrobial resistance prediction compared to broth microdilution were 90.8%, 90.1%, and 92.4% for E. coli (n = 1,095); 87.7%, 91.7%, and 90.6% for K. pneumoniae (n = 687); 95.5%, 98.9%, and 96.3% for methicillin-resistant S. aureus (n = 2,150); and 95.4%, 97.9%, and 97.2% for vancomycin-resistant Enterococcus faecium (n = 944). Additionally, this internal tool refinement identified areas of improvement for antimicrobial resistance prediction. The average sensitivity, specificity, and concordance of antimicrobial resistance prediction were high (>90%) for most combinations of antimicrobials and species that were evaluated. While AMR prediction from WGS was very promising, it did not correlate well with current Clinical and Laboratory Standards Institute breakpoints for non-susceptibility for some antimicrobial-organism combinations. As in silico prediction of antimicrobial resistance has been improved in this study through tool refinement, it shows future promise for molecular methods to complement phenotypic antimicrobial susceptibility testing. This will allow for more precise tracking of the molecular epidemiology of resistance and cost savings when isolates are being sequenced for strain typing.
    IMPORTANCE: In silico prediction of antimicrobial non-susceptibility in priority healthcare pathogens is becoming an important area of study due to the rising rates of resistance and the transition to whole-genome sequencing. To evaluate whether Staramr, an antimicrobial resistance (AMR) prediction tool, can reliably detect non-susceptibility in four top-priority healthcare-associated bacteria, we performed a validation study on a large Canadian clinical data set, which included carbapenemase-producing Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus. Compared to traditional antimicrobial susceptibility testing, we found that Staramr was reliable for predicting non-susceptibility for most combinations of antimicrobials and organisms; however, some combinations require additional data on genetic mechanisms of resistance for accurate prediction. Additionally, this study identified areas for refinement for current drug-gene interpretation keys. Thus, this tool refinement study advances the use of genotypic methods of AMR prediction for high-priority healthcare pathogens.
    Keywords:  Escherichia coli; Klebsiella pneumoniae; PointFinder; ResFinder; Staramr; antimicrobial resistance prediction; carbapenemase; methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococcus
    DOI:  https://doi.org/10.1128/spectrum.01652-26
  36. BMJ Paediatr Open. 2026 Oct 03. pii: e005154. [Epub ahead of print]10(1):
      The escalation of antibiotic-resistant organisms (AROs) represents a formidable challenge to clinical practice and public health globally. Within the landscape of Gram-positive pathogens, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci remain the most prevalent threats. Concurrently, the rise of Gram-negative AROs, including multidrug-resistant Escherichia coli, Klebsiella pneumoniae and carbapenem-resistant Enterobacterales, has severely curtailed available therapeutic options. These pathogens are associated with significant morbidity and mortality in neonatal intensive care units, where the combination of immunological immaturity and the requirement for invasive interventions places infants at heightened risk. This narrative review synthesises current evidence regarding the microbiology, evolving epidemiology and preventative strategies for AROs within neonatal healthcare settings.
    Keywords:  Infant; Intensive Care Units, Neonatal; Microbiology; Neonatology
    DOI:  https://doi.org/10.1136/bmjpo-2026-005154
  37. Front Microbiol. 2026 ;17 1943873
      Microbiome research has made substantial progress toward clinical translation over the past 2 decades, moving from associative observations toward mechanistic investigation, validation, and therapeutic intervention. This narrative review examines recent advances in the clinical application of microbiome research over the past 5 years, focusing on non-invasive microbiome-derived biomarkers and therapeutic strategies, including personalized probiotics and prebiotics, fecal microbiota transplantation (FMT), and engineered microbial therapeutics, while evaluating the strength of the supporting evidence. Microbiota-based treatments for recurrent Clostridium difficile infection are currently at the forefront of clinical translation, whereas applications in inflammatory, metabolic, neurological, and oncological disorders remain largely investigational. We further examine these translational barriers while highlighting opportunities to integrate microbiome data with systems biology and advanced analytics to improve clinical outcomes and advance precision medicine. By linking mechanistic discoveries with their current level of clinical development, this narrative review critically evaluates the available translational microbiome evidence, identifies key bottlenecks and unresolved knowledge gaps, and outlines priorities for the responsible integration of microbiome-based diagnostics and therapeutics into clinical practice.
    Keywords:  FMT; antimicrobial stewardship; engineered microbial therapies; gut microbiome; host–microbiome interactions; microbiome-based therapeutics; microbiota modulation; translational microbiome research
    DOI:  https://doi.org/10.3389/fmicb.2026.1943873
  38. Nat Commun. 2026 08 25. pii: 10475. [Epub ahead of print]17(1):
      Timely transition from intravenous to oral antibiotic therapy shortens hospital stays, reduces catheter-related infections, and lowers healthcare costs, yet one in five patients in England remain on intravenous antibiotics despite meeting switching criteria. Clinical decision support systems can improve switching rates, but approaches that learn from historical decisions reproduce the delays and inconsistencies of routine practice. We propose using neural processes to model vital sign trajectories probabilistically, predicting switch-readiness by comparing forecasts against clinical guidelines rather than learning from past actions, and ranking patients to prioritise clinical review. The design yields interpretable outputs, adapts to updated guidelines without retraining, and preserves clinical judgement. Validated on datasets from US intensive care (6333 encounters) and a UK academic hospital group (10,584 encounters), the system selects 2.2-3.2 × more relevant patients than random. We show that forecasting patient physiology offers a principled foundation for decision support in antibiotic stewardship.
    DOI:  https://doi.org/10.1038/s41467-026-76715-w