bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–09–06
forty-six papers selected by
Luca Bolliger, lxBio
  1. Artificial Intelligence Applications in Bacteriophage Genomics and Host Interaction.
  2. First UK use of bacteriophage therapy with DAIR for chronic Staphylococcus aureus prosthetic joint infection.
  3. Using bacteriophage cocktails in MDR Gram-negative infections: a practical manual.
  4. Non-antibiotic treatments for the management of recurrent urinary tract infection in the multidrug resistance era: A narrative review.
  5. Is Phage Therapy the Next Big Hope for Urinary Tract Infections?
  6. Transforming wound care: the role of AI in achieving clinical and financial outcomes.
  7. From Saprophyte to Pathogen: Multidrug-Resistant Pseudomonas fluorescens Wound Infection in Two Patients.
  8. Genomic and phenotypic characterization of Klebsiella pneumoniae phage KP Ø1: a novel lytic Slopekvirus targeting uropathogenic multidrug-resistant Klebsiella pneumoniae.
  9. Bacterial Lysis Observation Over Time Assay (BLOTS) for High-Throughput Isolation, Sequencing, and Characterization of Bacteriophages.
  10. Editorial: Phage-based interventions in livestock: from genomics to translational applications.
  11. Design and evaluation of a phage cocktail to control agriculture-associated multidrug-resistant Escherichia coli contamination on lettuce.
  12. A Lytic Bacteriophage Cocktail Attenuates Carbapenem-Resistant Klebsiella pneumoniae-Acinetobacter baumannii Mixed-Species Biofilms and Reshapes Transcriptional Responses.
  13. Periodontitis and Neuropsychiatric Disorders: Epidemiological and Mechanistic Evidence.
  14. Achromobacter species in cystic fibrosis and chronic lung disease: a review of virulence, antibiotic resistance, diagnostic challenges, and emerging therapies.
  15. The Oral Microbiome: A Silent Contributor to Systemic Health and Disease National Institutes of Health 2024 Workshop.
  16. Microbial exposure and host responses to infection reshape the disease trajectory of MASLD.
  17. The gut reservoir of carbapenem-resistant Enterobacterales: from dysbiosis and colonization to infection and decolonization, with a focus on patients with hematologic malignancies - a narrative review.
  18. Drug-resistant bacterial infections in end-stage liver disease: immune imbalance and intervention advances.
  19. Wound care and the NHS 10-year health plan: aligning clinical innovation with system value.
  20. Bacteriophages as emerging modulators of antitumor immunity in the tumor microenvironment.
  21. Next-generation anti-infective drugs in the post-antibiotic era: focusing on anti-virulence agents targeting the bacterial quorum sensing system.
  22. Small serine recombinases are markers for antiphage defense system discovery.
  23. Pharmacological Targets for Periodontitis: A Systematic Review of Drug-Target Mendelian Randomisation Studies.
  24. From Mouth to Mind: Unraveling the Oral Microbiome's Role in Orofacial Pain and Neurodegeneration.
  25. Multiobjective learning and design of bacteriophage specificity.
  26. Carbapenem-resistant and other multidrug-resistant organisms in a South Indian tertiary care centre: A laboratory-based study.
  27. Phage vB_KpnM_NB cocktail synergizing with amikacin in inhibiting persister cells of Klebsiella pneumoniae.
  28. Evolutionary dynamics and research hotspots of phage applications against Klebsiella pneumoniae infections from the past to the new era.
  29. Does teamwork make the dream work? A scoping review of multidisciplinary teams in pressure injury prevention and management.
  30. 16S rRNA sequencing and conventional culture provide complementary information in hospitalized patients with chronic lower-limb wounds.
  31. Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.
  32. Methicillin resistant staphylococcus aureus treatment and control in neonates: lessons learned - a Vietnam perspective.
  33. Caregiver Burden Mediates the Association Between Patient Self-Care Behaviors and Psychological Distress in Diabetic Foot Ulcer Care.
  34. The airway microbiome in asthma.
  35. AI-Enhanced System for Diabetic Foot Ulcer Localization and Classification Using Multi-Scale Neural CNN Model.
  36. Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.
  37. The cystic fibrosis gut microbial dysbiosis index (CF-GMDI): a quantitative measure of gut microbial imbalance in children with cystic fibrosis.
  38. Antimicrobial photodynamic therapy across ESKAPE pathogens: Efficacy, limitations, and a pathogen-adapted framework toward clinical translation.
  39. AResKGLM: a graph-grounded language-model framework for interpretable multi-hop antimicrobial resistance reasoning.
  40. Outer membrane vesicles in Pseudomonas aeruginosa pathogenesis: a systematic review of virulence dissemination, immune modulation, and antimicrobial resistance, with perspectives for veterinary and one health practice.
  41. The oral microbiome and dental health during pregnancy: Impact on maternal and foetal health outcomes.
  42. Collagen-based dressings for diabetic foot ulcers: A systematic review.
  43. Editorial: Innovative biologics in the battle against bacterial pathogens: disrupting pathogenesis with precision.
  44. CFTR Modulator Therapy and Aerobic Fitness Changes in Aerobic Fitness Following Initiation of CFTR Modulator Therapy: A Systematic Review and Meta-Analysis.
  45. Uncovering the mechanism of action of a historical antimicrobial against S. aureus and A. baumannii.
  46. Tetracyclines, a timely resurgence or doomed to fail again?
  1. Methods Mol Biol. 2026 ;3058 439-466
    Artificial Intelligence Applications in Bacteriophage Genomics and Host Interaction.
    M Fernanda Vieira, Hugo Oliveira, Oscar Dias, Miguel Rocha.
      Antibiotic-resistant bacterial infections remain a major public health challenge, contributing to an estimated 1.27 million deaths in 2019. Pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, cause a range of infections in clinical and food environments. As these bacteria rapidly develop resistance to multiple antibiotics, there is a growing need for alternative treatments. One promising approach is bacteriophage (phage) therapy. Phages are bacterial viruses that recognize, infect, and kill their hosts to propagate. Their relatively low isolation and production costs make them attractive antibacterial agents. However, unlike antibiotics, their host specificity requires individualized testing to identify effective phages, typically through plaque assays. This labor-intensive and time-consuming method limits the scalability of phage therapy, especially for large phage libraries. With the remarkable advances in genome sequence technologies over the past years, a vast and highly diverse set of phage genomes have been sequenced at decreasing costs. This growing volume of genomic data has enabled the application of Artificial Intelligence (AI), particularly Machine Learning (ML), and its subfield Deep Learning (DL) in phage research. Data-driven approaches are increasingly used for genome annotation, host prediction, lifestyle classification, and the identification of therapeutic candidates, offering scalable alternatives to traditional methods. Despite the availability of numerous genome annotation tools, only a limited number are specifically tailored to phage genomes. Phage infectivity, determined by host range, arises from complex interactions between the phage and its host at both extracellular and intracellular levels. Extracellularly, successful infection depends on the phage's ability to recognize and bind to host receptors. Intracellularly, bacteria have evolved a variety of innate and adaptive defense systems to prevent phage replication. To better understand these interactions, several computational tools have been developed to detect and characterize phage-host interactions. A comprehensive understanding of phage-host dynamics, both extracellular and intracellular level, is critical for advancing predictive models and facilitating the clinical translation of phage therapy.
    Keywords:  Bacteriophages; Defense mechanisms; Machine learning; Phage annotation; Phage therapy; Phage–host interaction
    DOI:  https://doi.org/10.1007/978-1-0716-5408-8_18
  2. ASM Case Rep. 2026 Sep;pii: e00082-26. [Epub ahead of print]2(5):
    First UK use of bacteriophage therapy with DAIR for chronic Staphylococcus aureus prosthetic joint infection.
    A Scobie, T Ferry, D Roulston, S Subbarao, T Thai, G Trafford, A Cudmore, J Miles, K Crick, S H Chin, R Lester, S Warren, N Karunaharan, P-J Ceyssens, M Merabishvili, S Djebara, J-P Pirnay, T Azamgarhi.
       Background: Chronic Staphylococcus aureus prosthetic joint infection (PJI) remains difficult to manage when surgical revision and long-term antibiotics are not feasible. Bacteriophage therapy is emerging as a potential adjunct, though experience in orthopedic infections, particularly in the United Kingdom, is limited.
    Case Summary: We report the first UK case of intra-articular bacteriophage therapy administered alongside debridement, antibiotics, and implant retention (DAIR) for chronic methicillin-sensitive Staphylococcus aureus knee PJI. An 81-year-old man with multiple comorbidities developed persistent infection following revision knee arthroplasty, with recurrent sinus formation despite multiple surgical washouts and prolonged suppressive antibiotics. Major revision surgery and amputation were not viable options. Following a multidisciplinary review through the UK Clinical Phage Network, targeted phage therapy was pursued as salvage treatment. Phage susceptibility testing identified an active lytic phage (ISP). The patient underwent open DAIR with intra-articular phage administration, adjunctive local antibiotics, short-course intravenous antimicrobials, and subsequent oral suppressive therapy. Two further intra-articular phage doses were administered postoperatively. Initial sinus closure occurred, but recurrence developed within 4 weeks. At 18 months, symptoms were partially improved with better mobility and reduced inflammation, though one sinus tract persisted. No significant adverse effects were observed. Whole-genome sequencing of pretreatment isolates demonstrated a predominantly ST5 S. aureus genotype with conserved biofilm-associated virulence genes and limited antimicrobial resistance in addition to clonal diversification consistent with chronic biofilm infection.
    Conclusion: This case demonstrates the feasibility and safety of intra-articular phage therapy during DAIR in a UK setting but highlights biological, logistical, and pharmacological factors that may limit efficacy in advanced chronic PJI.
    Keywords:  Staphylococcus aureus; antimicrobial resistance; bacteriophage or phage therapy; prosthetic joint infection; salvage therapy
    DOI:  https://doi.org/10.1128/asmcr.00082-26
  3. Curr Opin Infect Dis. 2026 Aug 27.
    Using bacteriophage cocktails in MDR Gram-negative infections: a practical manual.
    Jennifer M Dan.
       PURPOSE OF REVIEW: Bacteriophage therapy is a promising treatment on the horizon for multidrug resistant (MDR) and difficult-to-treat infections.
    RECENT FINDINGS: There have been a number of case reports and case series using bacteriophages to treat MDR infections. This has sparked interest by many patients and providers in accessing this treatment. However, the timeline from start of screening for phages to quality control in manufacturing to regulatory applications and the actual administration can be quite long. It is therefore important to be realistic with persons seeking treatment. Bacteriophage therapy is in its infancy. We are only beginning to understand the pharmacokinetics and pharmacodynamics of phages and how the development of phage-specific immune response may impact efficacy. Patients do develop neutralizing antibodies against bacteriophages. This is akin to someone receiving a first-time vaccination or first-time exposure to a viral infection. These neutralizing antibodies have the potential to impede efficacy, particularly if treatment extends past the 14-day window during which a patient first seroconverts from an IgM response to an IgG response. Finally, bacteriophages are useful tools to disrupt biofilms in patients with recurrent urinary tract infections, pulmonary infections, and those with retained hardware.
    SUMMARY: Understanding the protocol for phage therapy in addition to the potential setbacks is essential to eventually formulating "off-the-shelf" therapy.
    Keywords:  bacteriophage; multidrug resistant infection; phage cocktail
    DOI:  https://doi.org/10.1097/QCO.0000000000001237
  4. Investig Clin Urol. 2026 09;67(5): 403-412
    Non-antibiotic treatments for the management of recurrent urinary tract infection in the multidrug resistance era: A narrative review.
    Dong Soo Kim, Chang Il Choi, Jin Bong Choi, Taesoo Choi, Jeong Woo Lee.
      Recurrent urinary tract infections (UTIs) are a significant global health burden, increasingly complicated by antibiotic resistance. Traditional approaches with antibiotics increase the risk of multidrug-resistant (MDR) strains, emphasizing the need for new non-antibiotic treatments. Several promising approaches have emerged during the last decade. Microbiome-based therapies, including probiotics, asymptomatic bacteriuria strains, and fecal microbiota transplantation, aim to restore microbial balance. Immunomodulation, through cytokine targeting and bacterial vaccines, shows potential for boosting host defenses. Bacteriophage therapy offers precision targeting of MDR pathogens and biofilms. Nanoparticles enable targeted delivery and biofilm disruption through both organic and inorganic carriers. Additionally, agents like methenamine hippurate, D-mannose, estrogen, and cranberry extracts have shown varying degrees of efficacy and safety. These strategies represent essential steps toward sustainable UTI management, but most will require further clinical validation before their use in the general population.
    Keywords:  Bacteriophages; Immunomodulation; Microbiome; Nanoparticles; Urinary tract infection
    DOI:  https://doi.org/10.4111/icu.20250655
  5. JAMA. 2026 Sep 04.
    Is Phage Therapy the Next Big Hope for Urinary Tract Infections?
    Samantha Anderer, Jennifer Abbasi.
      
    DOI:  https://doi.org/10.1001/jama.2026.17683
  6. Br J Community Nurs. 2026 Sep 02. 31(9): 449-453
    Transforming wound care: the role of AI in achieving clinical and financial outcomes.
    Jackie Stephen Haynes, James Burford.
      Wound care has significant associated challenges in clinical practice, particularly for chronic wounds such as venous leg ulceration, pressure ulceration and diabetic foot ulceration. This article discusses the emerging and current applications of artificial intelligence in wound care, including wound image analysis, infection detection, predictive modelling and decision support systems. The article explores how artificial intelligence technologies are being leveraged to enhance accuracy and efficiency in wound assessment and management. Additionally, the integration of artificial intelligence with mobile health platforms and wearable devices is examined, particularly in the context of telehealth and remote patient monitoring. Consideration is given to the challenges of artificial intelligence including data quality, algorithm bias, ethical concerns and regulatory challenges. Clinicians may be able to apply artificial intelligence safely and effectively to their own clinical practice. Direction for future research is also identified.
    Keywords:  algorithm; artificial intelligence; technology; telehealth; wound assessment; wound care
    DOI:  https://doi.org/10.12968/bjcn.2026.0014
  7. Indian J Med Microbiol. 2026 Sep 03. pii: S0255-0857(26)00238-0. [Epub ahead of print] 101279
    From Saprophyte to Pathogen: Multidrug-Resistant Pseudomonas fluorescens Wound Infection in Two Patients.
    Karthi Jayakumar, J Janani, K Shakthy, K Sandeep, K T Sharuka.
      Pseudomonas fluorescens, an environmental rhizobacterium, is a rare cause of human wound infection. We describe two patients: a 73-year-old man with a 6-month diabetic foot ulcer, and a 30-year-old woman with a 2-month foot ulcer, whose wound swabs yielded multidrug-resistant P. fluorescens in pure culture. Identification relied on standard phenotypic methods, including pyoverdine fluorescence on King's B medium; molecular confirmation was not performed. Both isolates were meropenem-susceptible. Both patients received targeted intravenous meropenem with debridement and wound care, improving clinically, with culture-confirmed clearance in one. Susceptibility-guided therapy is essential given this organism's intrinsic resistance.
    Keywords:  Pseudomonas fluorescens; colonisation; multidrug resistance; pseudobacteremia; wound infection
    DOI:  https://doi.org/10.1016/j.ijmmb.2026.101279
  8. Sci Rep. 2026 Sep 03. pii: 27778. [Epub ahead of print]16(1):
    Genomic and phenotypic characterization of Klebsiella pneumoniae phage KP Ø1: a novel lytic Slopekvirus targeting uropathogenic multidrug-resistant Klebsiella pneumoniae.
    Reham Fadl, Ghada Ismail, Ahmed Elshafei, Amira Mohamed Mokhtar, Omnia Mohamed El Nabawy, Mohamed Gomaa Seadawy, Mahmoud M Baraka, Basma Sherif.
      The rise of multidrug-resistant (MDR) uropathogenic gram-negative bacteria (GNB) necessitates the development of alternative therapeutic strategies. This study aimed to isolate, phenotypically characterize, and perform whole-genome sequencing of the bacteriophage demonstrating the broadest host range against MDR uropathogens. Fifty MDR GNB isolates were screened for lytic phages. The most promising candidate, Klebsiella pneumoniae phage KP Ø1, was characterized using plaque assay, Transmission Electron Microscopy (TEM), and pH/thermal stability testing. Genomic characterization was performed via whole-genome sequencing (WGS), with functional annotation and lifestyle prediction using PhaBOX and PhageScope software. Klebsiella pneumoniae was the most prevalent MDR uropathogen. Klebsiella pneumoniae phage KP Ø1 exhibited a 50% host range and high lytic titer (10⁸ PFU/mL). TEM revealed an icosahedral head and short contractile tail. Genomic characterization by WGS revealed that Klebsiella pneumoniae phage KP Ø1 possesses a 174,591 bp double-stranded deoxyribonucleic acid (dsDNA) genome containing 274 predicted open reading frames (ORFs). No lysogeny-related genes, toxins, or antibiotic resistance markers were detected, confirming its strictly lytic nature and supporting its potential as a candidate for phage therapy applications. The phage remained stable (10⁸ PFU/mL) across temperatures of - 20 °C to 50 °C; supporting its suitability for long-term biobanking and suggesting potential activity at physiological temperature, and across a pH range of 7-9. Klebsiella pneumoniae phage KP Ø1 is a novel, obligately lytic Slopekvirus whose genomic architecture, stability profile, and absence of lysogeny-associated, virulence, and antimicrobial resistance genes ( AMR) collectively support its candidacy for further preclinical evaluation as a phage therapy agent against uropathogenic MDR Klebsiella pneumoniae.
    Keywords:   Klebsiella pneumoniae ; Slopekvirus ; Genomic characterization; MDR uropathogens; Phage therapy
    DOI:  https://doi.org/10.1038/s41598-026-67695-4
  9. Curr Protoc. 2026 Sep;6(9): e70454
    Bacterial Lysis Observation Over Time Assay (BLOTS) for High-Throughput Isolation, Sequencing, and Characterization of Bacteriophages.
    Sean Jia Le Pang, Soon Keong Wee, Bobby Guo Wei Lee, Odelia Yap, Eric Peng Huat Yap.
      Phages remain severely under-sampled, largely due to the limitations of current isolation methods, which are labor-intensive, low-throughput, and often restricted to a narrow set of bacterial hosts. To address this gap, we developed a robust and scalable field-to-genome workflow that leverages laboratory automation to screen environmental samples against a comprehensive 188-strain bacterial host library using a 384-well plate format. We demonstrate the workflow using Acinetobacter baumannii as the primary model host. Phage activity is detected through Bacterial Lysis Observation over Time assay (BLOTS) using spectrophotometry. Subsequently, isolation and subculture of the phages are done with a single layer agar spot assay. Phage genomes are then sequenced using long-read technology and annotated. This enables systematic and reproducible phage detection and enrichment from diverse sample types. The use of large numbers of host strains streamlines phage discovery and substantially increases the chances of isolating novel phages. The BLOTS high-throughput approach can also be used for screening phage collections against specified clinical hosts of interest for phage research and candidate selection for phage therapy applications. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of host libraries and multi-host primary enrichment Basic Protocol 2: Preparation of the BLOTS screening plate using an automated liquid handler Alternate Protocol 1: Manual phage screening without laboratory automation Basic Protocol 3: Phage screening using BLOTS Basic Protocol 4: Phage validation using the single-layer agar spot assay Basic Protocol 5: Phage amplification for downstream applications Basic Protocol 6: Phage concentration using PEG-8000 precipitation Alternate Protocol 2: Phage concentration using centrifugal filtration Basic Protocol 7: Automated DNA extraction with magnetic beads Basic Protocol 8: Whole-genome sequencing using long reads Basic Protocol 9: De novo genome assembly using the Phage Galaxy platform Basic Protocol 10: Annotation and characterization of phage genome Basic Protocol 11: Host range testing and characterization of isolated phages using BLOTS.
    Keywords:  bacteriophage; high‐throughput screening; host range; isolation; laboratory automation; phage therapy; sequencing
    DOI:  https://doi.org/10.1002/cpz1.70454
  10. Front Microbiol. 2026 ;17 1944669
    Editorial: Phage-based interventions in livestock: from genomics to translational applications.
    Sonia Zapata-Mena, Christian Vinueza-Burgos, William Calero-Cáceres.
      
    Keywords:  genomics; livestock; omics; phage (bacteriophage); phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2026.1944669
  11. Int J Food Microbiol. 2026 Aug 31. pii: S0168-1605(26)00417-4. [Epub ahead of print]462 112036
    Design and evaluation of a phage cocktail to control agriculture-associated multidrug-resistant Escherichia coli contamination on lettuce.
    Eunbyeol Ahn, Joonbeom Kim, Hojun Shin, Yerin Jin, Sumin Son, Seungjo Ko, Sangryeol Ryu.
      Multidrug-resistant (MDR) Escherichia coli from agricultural environments is an emerging threat to food safety and public health. Bacteriophages have emerged as promising alternatives to antibiotics for controlling MDR bacteria. However, studies evaluating phage biocontrol against phenotypically characterized MDR E. coli isolates from agricultural environments remain limited. This study aimed to characterize E. coli isolates recovered from agricultural environments and to develop and evaluate a phage cocktail against a target MDR isolate. A total of 11 E. coli strains were isolated and assessed for antibiotic susceptibility, biofilm formation, and swimming motility. Among them, KAE09 was selected as the target MDR isolate based on its resistance to multiple antibiotics, including streptomycin, tetracycline, oxolinic acid, and ciprofloxacin, together with strong biofilm-forming ability and high motility. To control this isolate, we developed a phage cocktail consisting of two E. coli phages, ELP2 and ELT3, with previously reported distinct receptor specificities. Cross-resistance analysis showed no reciprocal cross-resistance between ELP2 and ELT3 in KAE09. The phage cocktail significantly inhibited bacterial growth, reduced preformed biofilms, and suppressed biofilm formation of KAE09. The cocktail also effectively reduced viable cell counts of the isolate on lettuce at room temperature and under refrigeration. These findings highlight the potential of the phage cocktail as an effective biocontrol agent for reducing MDR E. coli contamination on fresh produce.
    Keywords:  Biocontrol; Biofilm; Food safety; Multidrug-resistant Escherichia coli; Phage cocktail
    DOI:  https://doi.org/10.1016/j.ijfoodmicro.2026.112036
  12. Microb Biotechnol. 2026 Sep;19(9): e70439
    A Lytic Bacteriophage Cocktail Attenuates Carbapenem-Resistant Klebsiella pneumoniae-Acinetobacter baumannii Mixed-Species Biofilms and Reshapes Transcriptional Responses.
    Xuefang Ren, Rui Zhu, Yijiang Yang, Xiaojuan You, Liuxiang Wang, Guangyu Fu, Yehuan Zheng, Chunxia Wang, Zhentao Wang, Yongwei Li.
      Mixed-species biofilms formed by carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii can complicate the clinical management of device-associated infections; however, phage-based interventions targeting these communities remain insufficiently characterized. We assessed the antibiofilm activity of a lytic HZJ31 + HZY2308 phage cocktail against KPZ2-AB48 mixed-species biofilms. Compared with the corresponding single-species cultures, cocultures showed greater crystal violet-stained biomass, higher metabolic activity as measured by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay, and microscopic surface coverage. Phage-cocktail exposure during biofilm development or after biofilm formation reduced biomass, XTT reduction, culturable bacterial counts, and scanning electron microscopy-derived surface coverage, with similar changes observed on central venous catheter surfaces. In Galleria mellonella infection models, cocktail treatment increased survival and was associated with less extensive histopathological lesions and lower Kirschner wire-associated bacterial burdens. RNA sequencing and quantitative reverse transcription polymerase chain reaction identified treatment-associated transcriptional changes involving metabolic pathways, autoinducer-2 transport, cell-envelope functions, efflux systems, and stress responses. These findings support further preclinical investigation of phage cocktails targeting multidrug-resistant mixed-species biofilms.
    DOI:  https://doi.org/10.1111/1751-7915.70439
  13. J Periodontal Res. 2026 Sep 04.
    Periodontitis and Neuropsychiatric Disorders: Epidemiological and Mechanistic Evidence.
    Julia Ríos-Barbero, María Martínez, Nagore Ambrosio, Borja García-Bueno, David Fraguas, Juan Carlos Leza, Mariano Sanz, Elena Figuero.
      This review aims to critically analyze the epidemiological evidence and mechanistic insights linking periodontitis with the onset, progression, or severity of neuropsychiatric disorders. From an epidemiological perspective, eligible evidence was identified regarding disorders related to trauma, stress, anxiety, depressive, and bipolar disorders, whereas no studies meeting the predefined inclusion criteria were found for the remaining considered disorders. The strongest epidemiological evidence was observed for depressive disorders and anxiety- and stress-related conditions. However, the predominance of cross-sectional studies, together with substantial methodological heterogeneity, limits conclusions regarding temporality and causality. From a mechanistic perspective, the available evidence regarding the association between periodontitis and neuropsychiatric disorders predominantly supports as mechanisms (1) microbial pathways (microbial translocation and functional dysregulation of the oral microbiome), (2) inflammatory and immune pathways (systemic (meta)inflammation and trafficking of immune players systemic), and (3) shared underlying vulnerabilities (behavioral factors, medication-related effects, lifestyle and systemic health factors, and genetic mechanisms). Periodontitis may promote a persistent low-grade systemic inflammatory state through the release of bacterial products and inflammatory mediators into the circulation, thereby influencing immune, neuroendocrine, and vascular pathways relevant to neuropsychiatric vulnerability. Moreover, the hematogenous dissemination or swallowing of periodontal bacteria and their virulence factors may contribute to microbial remodeling at distant sites, including the gut, supporting the concept of an oral-gut-brain axis. Overall, the evidence analyzed supports periodontitis as a potential modifiable contributor within a broader biopsychosocial network linking oral and mental health, while highlighting the need for longitudinal studies and interventional trials to clarify causality and clinical relevance.
    Keywords:  neuroinflammation; neuropsychiatric disorders; oral–brain axis; periodontal diseases; periodontal medicine; periodontitis; systemic inflammation
    DOI:  https://doi.org/10.1111/jre.70172
  14. Ther Adv Respir Dis. 2026 Jan-Dec;20:20 17534666261471308
    Achromobacter species in cystic fibrosis and chronic lung disease: a review of virulence, antibiotic resistance, diagnostic challenges, and emerging therapies.
    Bandar Hasan Saleh, Jawahir A Mokhtar, Dalya Attallah, Hatoon A Niyazi, Hanouf A Niyazi, Mona Abdulrahman Alqarni, Turki M Alharthi, Khulud A Alhazmi, Rawan Altalhi, Loui A Ismaeel, Sarah Almuhayya, Faye A Aldehalan, Wafaa Alhazmi, Hadeel Ahmed Alsufyani, Karem Ibrahem.
      Achromobacter species (spp) is an emerging opportunistic organism more frequently isolated from immunocompromised patients' and hospital settings. This bacterium was once considered an environmental bacterium, but now it is recognized as a serious cause of respiratory infections, bloodstream infections, and urinary tract infections, particularly among patients with cystic fibrosis (CF), chronic illnesses, and medical devices. The purpose of this review is to highlight Achromobacte's clinical significance, pathogenic mechanism, and recent approaches for diagnosis and treatment. By utilizing specific keywords relevant to Achromobacter spp., a comprehensive literature search was performed in PubMed and Google Scholar. To summarize existing knowledge and highlight gaps in the literature, peer-reviewed studies on clinical relevance, pathogenicity, antimicrobial resistance, and therapeutic approaches were gathered, screened, and narratively assembled. Among the 19 identified species, Achromobacter xylosoxidans (A. xylosoxidans) is the most prevalent and clinically relevant, especially in CF settings. This review explores the organism's microbiological characteristics, virulence strategies-including robust biofilm formation, motility, and secretion systems-and its alarming intrinsic and acquired resistance to antibiotics. Misidentification due to phenotypic overlap with other non-fermenting Gram-negative bacilli complicates diagnosis, while limited MALDI-TOF MS and database representation hinders species-level identification. Genotyping methods, including multi-locus sequence analysis and housekeeping gene sequencing, offer superior resolution but remain underutilized in clinical diagnostics. With rising resistance mediated by β-lactamases, efflux pumps, and adaptive genomic traits, Achromobacter spp presents a growing challenge for treatment and infection control. This review highlights the urgent need for improved diagnostic strategies, species-level clinical and microbiological data, and tailored therapeutic approaches to manage Achromobacter spp. infections effectively.
    Keywords:  A. xylosoxidans; Achromobacter; combination therapy; cystic fibrosis; phage therapy
    DOI:  https://doi.org/10.1177/17534666261471308
  15. Cancer Epidemiol Biomarkers Prev. 2026 Sep 01. 35(9): 1490-1494
    The Oral Microbiome: A Silent Contributor to Systemic Health and Disease National Institutes of Health 2024 Workshop.
    Gabriela Riscuta, Anil Wali, Emmanuel F Mongodin, Mukesh Verma, Marco Cardone, Hye-Sook Kim, Tamara McNealy, Altaf Mohammed.
      Previously considered primarily only in the context of dental diseases, the oral microbiome is now recognized as a contributor to a variety of systemic diseases, including cancer and cardiovascular diseases. This commentary explores the evolving view of the oral cavity as a gateway to the body's broader physiologic networks, implicating oral microbiome dysbiosis in a spectrum of chronic conditions. Drawing on current evidence, we propose a re-envisioned healthcare model that integrates oral and systemic health and outline research gaps and clinical priorities to harness the oral microbiome for preventive and therapeutic gains, emphasizing cancer-relevant biomarkers and intervention opportunities.
    DOI:  https://doi.org/10.1158/1055-9965.EPI-25-1553
  16. Front Cell Infect Microbiol. 2026 ;16 1932870
    Microbial exposure and host responses to infection reshape the disease trajectory of MASLD.
    Yunqi Zhang, Qingqing Xun, Shuyu Liu, Bo Zhuang, Meiyue Zang, Chengwei Tan, Yu Cui, Ruiji Li, Qianqian Zhang.
      Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major driver of the growing global burden of chronic liver disease and has attracted increasing attention because of its progressive hepatic outcomes. Metabolic syndrome-related factors, such as obesity and abnormal glucose metabolism, confer on MASLD both a risk of liver disease progression and systemic metabolic consequences. Evidence from observational studies and experimental models suggests that infection and microbial exposure may be associated with MASLD progression and may modify its clinical course through alterations in the gut-liver axis, enhanced immune activation, and amplification of metabolic inflammation. Meanwhile, the metabolic disturbances associated with MASLD can remodel the intestinal ecological niche and hepatic immune environment, impairing the host capacity to clear and regulate microbial signals and thereby altering infection susceptibility and clinical outcomes. Despite growing interest in infection and microbial dysbiosis in MASLD, most studies remain centered on individual pathogens. A unifying framework linking microbial exposure, host metabolic dysfunction, and inflammatory amplification is still lacking. For most infectious exposures, causal directionality and clinical modifiability remain uncertain. Accordingly, this review organizes the available evidence on the potential bidirectional relationships between infection and MASLD. It examines how gut-liver microbial signals, viral comorbidities, chronic colonization, and acute infection may shape the course of MASLD. It also considers how MASLD-related metabolic dysfunction may, in turn, modify host responses to infection. Overall, incorporating infection and microbial dysbiosis into the conceptual framework of MASLD may help move beyond a metabolism-centered explanatory model and identify priorities for future risk-stratification and intervention studies.
    Keywords:  dysbiosis; gut microbiota; gut–liver axis; host-microbe interactions; immunometabolism; infection; metabolic dysfunction-associated steatotic liver disease; microbial exposure
    DOI:  https://doi.org/10.3389/fcimb.2026.1932870
  17. Front Cell Infect Microbiol. 2026 ;16 1939690
    The gut reservoir of carbapenem-resistant Enterobacterales: from dysbiosis and colonization to infection and decolonization, with a focus on patients with hematologic malignancies - a narrative review.
    Lorenza Putignani, Riccardo Marsiglia, Luigia Turco, Antonio Russo, Stefania Pane, Alessandra Fusco, Loris Lopetuso, Enrico Maria Trecarichi.
      Carbapenem-resistant Enterobacterales (CRE) remain among the highest-priority antimicrobial-resistant pathogens worldwide, and intestinal colonization is increasingly recognized as the key precursor of invasive infections, particularly in patients with hematological malignancies. Increasing evidence indicates that disruption of the gut microbial ecosystem, reflected in reduced diversity, depletion of beneficial anaerobic taxa, intestinal barrier dysfunction, immune dysregulation, and expansion of Enterobacterales, plays a central role in the transition from colonization to infection. Consequently, restoring colonization resistance through microbiome-targeted interventions has emerged as a promising preventive strategy. This narrative review summarizes the current evidence on the epidemiology and clinical impact of CRE colonization and infection, with particular emphasis on the ecological alterations of the gut microbiome linking gut dysbiosis to epithelial barrier dysfunction, immune dysregulation, and loss of colonization resistance to CRE persistence and invasive infection. We critically discuss both conventional and emerging decolonization approaches, including selective digestive decontamination, probiotics, prebiotics and synbiotics, fecal microbiota transplantation (FMT), bacteriophage therapy, and CRISPR-Cas-based technologies, highlighting their mechanisms of action, available clinical evidence, and current limitations. Particular attention is given to patients with hematological malignancies, in whom the clinical need for effective decolonization strategies is greatest. Although FMT currently represents the most promising microbiome-based intervention, the available evidence remains heterogeneous and largely derived from small studies. Overall, durable and standardized decolonization strategies have yet to be established, underscoring the need for well-designed multicenter randomized clinical trials to define effective microbiome-directed approaches for preventing CRE-related infections in high-risk populations.
    Keywords:  carbapenem-resistant Enterobacterales; colonization resistance; fecal microbiota transplantation; hematologic patients; microbiota-based decolonization strategies
    DOI:  https://doi.org/10.3389/fcimb.2026.1939690
  18. Front Immunol. 2026 ;17 1888293
    Drug-resistant bacterial infections in end-stage liver disease: immune imbalance and intervention advances.
    Jing Liu, Jun Wu, Xin Zheng.
      Patients with end-stage liver disease (ESLD) face a markedly elevated risk of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. This vulnerability worsens prognosis and severely limits therapeutic options. The underlying mechanisms extend beyond hepatic synthetic and detoxification failure to encompass a complex and multifaceted state of immune dysfunction. In this review, we synthesize current evidence on how ESLD-associated immune defects drive susceptibility to drug-resistant infections. We examine key abnormalities across multiple interconnected domains: depletion and dysfunction of Kupffer cells, complement deficiency, T-cell exhaustion with regulatory T-cell expansion, disruption of the gut-liver axis, immunometabolic reprogramming driven by hyperammonemia and lactate accumulation, and upregulation of immune checkpoint molecules such as PD-1/PD-L1. These pathways collectively promote colonization, persistence, and therapeutic refractoriness of MDR pathogens. We also evaluate emerging therapeutic strategies targeting these immune defects, including checkpoint inhibitors, cytokine and cellular therapies, microbiome modulation, and metabolic interventions, while acknowledging the challenges that limit their clinical translation. By proposing an integrated framework that links distinct immune defects to MDR infection pathogenesis, we aim to guide the development of biomarker-driven, personalized immunomodulatory approaches that complement antimicrobial therapy and ultimately improve outcomes in this high-risk population.
    Keywords:  drug-resistant bacterial infection; end-stage liver disease; gut microbiota; immune checkpoint; immune dysfunction; immunometabolism
    DOI:  https://doi.org/10.3389/fimmu.2026.1888293
  19. Br J Community Nurs. 2026 Sep;31(Sup9): S24-S28
    Wound care and the NHS 10-year health plan: aligning clinical innovation with system value.
    Richard H Shorney, James Saunders.
      The NHS Fit for the Future 10 Year Health Plan published in July 2025, represents the most ambitious structural redesign of the health service for a generation. For wound care, this creates both significant challenges and considerable opportunities. This article examines how wound care products and services can be aligned with the strategic priorities of the 10-year plan, including three systemic shifts, in addition to value-based procurement reform and drug tariff changes. These changes will affect how wound care products already listed on drug tariff are assessed through a renewal process. This is a narrative review of policy documentation, including the 10-year health plan, NHS England procurement guidance and value-based procurement frameworks, supplemented by analysis of pilot programmes and regional exemplars. Wound care is uniquely positioned to demonstrate value across all three of the plan's strategic shifts: from hospital to community, from analogue to digital and from sickness to prevention. Value-based procurement and drug tariff reform offer practical mechanisms for realigning wound care commissioning with system outcomes. Wound care should be repositioned not as a clinical commodity but as a strategic system resource. Organisations and industry partners that can evidence system value, not just clinical efficacy, are best placed to benefit from this NHS transformation.
    Keywords:  MedTech innovation; NHS 10-year plan; drug tariff; neighbourhood health centre; value-based procurement; wound care
    DOI:  https://doi.org/10.12968/bjcn.2026.0091
  20. Microbiol Res. 2026 Aug 29. pii: S0944-5013(26)00264-8. [Epub ahead of print]314 128700
    Bacteriophages as emerging modulators of antitumor immunity in the tumor microenvironment.
    Xiaoyan Chen, Junfeng Zhang, Feng Gao, Huijun Du.
      The tumor microenvironment (TME) is increasingly recognized as a complex ecosystem shaped by dynamic interactions among tumor cells, immune cells, and microbial components. While growing evidence has established the microbiota as a key regulator of antitumor immunity and immunotherapy response, the contribution of bacteriophages, the most abundant biological entities within microbial communities, has remained largely overlooked. Recent studies suggest that bacteriophages are not merely passive regulators of bacterial populations but can actively modulate host immune responses and influence tumor-associated immune landscapes. In this review, we summarize emerging evidence suggesting that bacteriophages may influence antitumor immunity through both direct and indirect mechanisms. Evidence from immune-cell and non-cancer experimental systems indicates that phage nucleic acids can engage TLR9-dependent sensing and, for selected phages, STING-associated inflammatory signaling; however, the relevance of these pathways within human tumors remains to be established. Indirectly, phages may alter microbial community structure and metabolic outputs, which could influence systemic immune tone and the composition of immune infiltrates within the TME. We further discuss accumulating data linking phageome features with tumor progression and responses to immune checkpoint blockade and other cancer therapies. However, much of the available evidence remains preclinical, indirect, or correlative, and causal roles for endogenous phages in human tumor immunity still require further validation. Distinct from the putative ecological and immunological roles of naturally occurring phages, engineered bacteriophages are being developed as therapeutic platforms for cancer immunotherapy, including tumor-antigen display, targeted delivery of immune agonists, cytokines or nucleic acids, and combination strategies with existing treatments. Finally, we address key methodological, mechanistic, and safety challenges that must be overcome to translate phage-based immunomodulation into clinical applications. Collectively, this review highlights the phageome as an emerging regulatory layer of tumor immunity and a promising, yet underexplored, target for therapeutic intervention.
    Keywords:  Antitumor immunity; Bacteriophages; Cancer immunotherapy; Innate immune sensing; Microbiome; Phageome; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.micres.2026.128700
  21. Front Cell Infect Microbiol. 2026 ;16 1935576
    Next-generation anti-infective drugs in the post-antibiotic era: focusing on anti-virulence agents targeting the bacterial quorum sensing system.
    Xin Hu, Yang Yuan, Zhiyong Yang, Yiwen Chu, Ting Huang, Kelei Zhao.
      Antimicrobial resistance is a critical global public health challenge, with drug-resistant infections contributing to more than one million deaths annually. The widespread dissemination of multidrug-resistant bacteria poses a severe threat to the management of infectious diseases. Bacterial evolution via genetic mutation and horizontal gene transfer diminishes antimicrobial efficacy, often leading to therapeutic failure, increased morbidity and mortality. However, the development of novel antibiotics lags far behind the rapid evolution of drug-resistant bacteria. Therefore, scientists worldwide have committed to exploring alternative therapeutic strategies for bacterial infections. The key question is which strategy holds the greatest promise of addressing the predicament of traditional antibiotics and being recognized as "next-generation anti-infective drugs". This narrative review summarizes several of the most promising alternative treatment strategies against bacterial infections, emphasizing the core strengths and limitations of each strategy. A critical comparative analysis reveals that no single strategy can simultaneously satisfy the demands of acute therapy, broad patient coverage, and resistance evasion, underscoring the need for context-dependent and sequential deployment. Moreover, among these alternatives, anti-virulence therapeutic strategies, particularly those targeting the bacterial quorum sensing (QS) system, represent a major and extensively studied approach, although their clinical translation remains nascent. This review delineates the molecular mechanisms and therapeutic potential of QS-targeting anti-virulence agents. Furthermore, we candidly assess the extant biological, pharmacological, and clinical barriers impeding their clinical translation, providing perspectives on future research directions to harness these next-generation anti-infective paradigms effectively.
    Keywords:  alternative therapeutic; anti-virulence agents; antimicrobial resistance; quorum sensing; quorum sensing inhibitors
    DOI:  https://doi.org/10.3389/fcimb.2026.1935576
  22. PLoS Biol. 2026 Aug 31. 24(8): e3003991
    Small serine recombinases are markers for antiphage defense system discovery.
    Shelby E Andersen, Joshua M Kirsch, Navtej Singh, Stephen R Garrett, John C Whitney, Jay R Hesselberth, Breck A Duerkop.
      Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.
    DOI:  https://doi.org/10.1371/journal.pbio.3003991
  23. J Periodontal Res. 2026 Sep 02.
    Pharmacological Targets for Periodontitis: A Systematic Review of Drug-Target Mendelian Randomisation Studies.
    Luigi Nibali, Jing Kang, Simon Haworth, Alessandro Polizzi, Gaetano Isola.
       AIM: Drug-target Mendelian randomisation (MR) studies investigate whether genetically proxied modulation of druggable proteins affects the risk of periodontitis, thereby identifying potential pharmacological targets.
    METHODS: A systematic review was conducted following PRISMA 2020 guidelines. Three electronic databases (MEDLINE/Pubmed, Scopus, Web of Science) were searched. Eligible studies applied MR to evaluate causal relationships between druggable targets and periodontitis. Data on study design, population, exposure, and outcomes were extracted; risk of bias was assessed qualitatively. Supplementary searches of Google Scholar, reference lists, and medRxiv were also undertaken.
    RESULTS: Fifteen MR studies published between 2023 and 2026 were included. Underlying data on periodontal outcomes were derived from a limited number of studies. Identified targets spanned inflammatory cytokines (e.g., IL6R), complement components (C3 and C5), immune regulators (CXCL10 and CXCR4), calcium-binding proteins (S100A8/A9/A12), and proteins involved in angiogenesis, apoptosis, cell-cycle regulation, and extracellular-matrix remodelling, including VEGFA, CASP3, CCND1, and MMP25. Several studies integrated multi-omics, colocalization, and single-cell approaches. However, the therapeutic relevance of these targets remains to be established through independent replication and experimental or clinical validation.
    CONCLUSION: Drug-target MR provides a platform for investigating host molecular traits linked to periodontal disease and highlights multiple targets for possible drug repurposing in the future. Methodological and data constraints currently limit the validity of these findings and their potential clinical applications.
    Keywords:  cytokine; drug; inflammation; mendelian; periodontitis
    DOI:  https://doi.org/10.1111/jre.70168
  24. J Clin Pract Res. 2026 Aug;48(4): 356-367
    From Mouth to Mind: Unraveling the Oral Microbiome's Role in Orofacial Pain and Neurodegeneration.
    Sanjana Moses, Tushar Phulambrikar, Tanvi Dosi.
      The human oral cavity hosts a diverse and dynamic microbiome comprising more than 700 microbial species, which plays a crucial role in maintaining oral and systemic health. Oral dysbiosis, defined as disruption of this microbial balance, has been increasingly implicated not only in periodontal disease but also in the pathogenesis of orofacial pain and neurodegenerative diseases. Key pathogens, such as Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum, have been proposed to release virulence factors, including lipopolysaccharides and gingipains, which may activate immune pathways and nociceptors, thereby driving peripheral sensitization and neuroinflammation. These organisms have also been suggested to breach mucosal and vascular barriers, enter the systemic circulation, and, in some cases, access the central nervous system. Evidence has linked oral pathogens to Alzheimer's disease, Parkinson's disease, autism spectrum disorder, and multiple sclerosis. Notably, P. gingivalis and its gingipains have been identified in postmortem brain tissue from patients with Alzheimer's disease, with proposed roles in neuroinflammation and amyloid plaque formation. Salivary microbial alterations in burning mouth syndrome and temporomandibular disorders further highlight the influence of the oral microbiome on neuropathic pain. Therefore, the oral-gut-brain axis represents a novel and promising area of investigation, offering potential diagnostic biomarkers and targeted microbial therapies for the management of chronic orofacial pain and neurological disorders.
    Keywords:  Brain-gut axis; microbiota-gut-brain axis; neurodegenerative diseases; neuroinflammation; orofacial pain; periodontal pathogens
    DOI:  https://doi.org/10.14744/cpr.2026.15313
  25. Cell Syst. 2026 Sep 01. pii: S2405-4712(26)00194-8. [Epub ahead of print] 101712
    Multiobjective learning and design of bacteriophage specificity.
    Naia Novy, Phil Huss, Sarah Evert, Philip A Romero, Srivatsan Raman.
      Proteins are often optimized for single functions during design and engineering without the consideration of other functionalities that may interfere with the intended outcome. Here, we apply deep learning to understand and design the multifunctional host-targeting landscape of the T7 bacteriophage receptor-binding protein for enhanced infectivity, predefined specificity, and high generality toward unseen strains. We compare four model architectures and experimentally characterize engineered phages optimized for 26 tasks. With multiobjective machine learning, it is possible to engineer complex specificities at success rates that enable low-throughput validation of predicted hits. The targeting capabilities of T7 are highly plastic, with opposite specificities occasionally separated by only a few mutations. This tunability underscores how models trained on multifunctional data can uncover key principles of phage biology and specificity. The same framework can guide multiobjective optimization of other proteins or biological systems, offering a general strategy for modeling multifunctional landscapes.
    Keywords:  T7; bacteriophage; deep mutational scanning; host specificity; machine learning; multiobjective optimization; phage engineering; protein engineering; protein language model; receptor-binding protein
    DOI:  https://doi.org/10.1016/j.cels.2026.101712
  26. Indian J Med Res. 2026 Sep;pii: 10.25259/IJMR_103_2026. [Epub ahead of print]164(3): 445-452
    Carbapenem-resistant and other multidrug-resistant organisms in a South Indian tertiary care centre: A laboratory-based study.
    Arya S Kumar, Sanjeev K Singh, Meera Susan John, Shreya H, Nimi Mohan, Irine Anna Sebastain, Vaishnavi S.
      Background and objectives Carbapenem-resistant gram-negative pathogens are associated with limited treatment options and poor clinical outcomes. This study assessed the prevalence, distribution, antimicrobial susceptibility, and clinical outcomes of multidrug-resistant organisms from intensive care units and related wards in a South Indian tertiary care hospital over three years. Methods A retrospective laboratory-based study was conducted between October 2022 to May 2025, analysed culture-positive specimens from the selected locations using hospital information system data. Multidrug-resistant organisms were defined according to international criteria. Organisms included carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., and trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia. Demographics, specimen distribution, antimicrobial susceptibility, and outcomes were analysed using descriptive and inferential statistics. Results Of 8,704 specimens processed, 3,450 (39.6%) were culture-positive and 750 (34.2%) were multidrug-resistant. Carbapenem-resistant Enterobacterales accounted for (n=490,65.3%) of multidrug-resistant organisms, followed by carbapenem-resistant Acinetobacter baumannii (n=85,11.3%), carbapenem-resistant Pseudomonas aeruginosa (n=85,11.3%), methicillin-resistant Staphylococcus aureus (n=40,5.3%), vancomycin-resistant Enterococcus spp. (n=34,4.5%), and trimethoprim-sulfamethoxazole-resistant S. maltophilia (n=16,2.1%). Klebsiella pneumoniae predominated among carbapenem-resistant Enterobacterales isolates. Multidrug-resistant organisms were significantly more common in intensive care units (539/750,71.9%) and among patients aged >60 y (399/750,53.2%) (P<0.05). Enterobacterales showed high resistance to cephalosporins and fluoroquinolones, while A. baumannii demonstrated limited meropenem susceptibility (18/110,16.3%). Overall mortality among patients with multidrug-resistant infections was (191/750,25.5%), with 94% (180/191) of deaths clinically attributed to infection. Interpretation and conclusions Carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii are the predominant multidrug-resistant organisms, especially in intensive care units. These highlights the urgent need for strengthened antimicrobial stewardship, infection-control practices and ongoing antimicrobial resistance surveillance.
    Keywords:  Antibiotic resistance; Antimicrobial stewardship; Carbapenem-resistant Enterobacterales; Multidrug-resistant organisms
    DOI:  https://doi.org/10.25259/IJMR_103_2026
  27. Appl Environ Microbiol. 2026 Sep 03. e0136726
    Phage vB_KpnM_NB cocktail synergizing with amikacin in inhibiting persister cells of Klebsiella pneumoniae.
    Bingqing Xu, Mengye Ma, Yiping Wang, Xingyu Li, Jieting Pan, Yi Jin, Ruiqin He, Lijian Ding, Liming Jiang.
      The emergence of multidrug-resistant Klebsiella pneumoniae (KPN) and antibiotic-tolerant persister cells poses a significant challenge to existing anti-infection therapies. Given the urgent need for sustainable alternatives to antibiotics, phage cocktails are emerging as a promising alternative to control K. pneumoniae infections. We isolated three lytic phages vB_KpnM_NB (1-3) from Ningbo environmental samples, classified them into the Drexlerviridae family, and determined the biological characteristics of two representative phages. Genomic analysis confirmed that these phages are closely related and lack resistance and virulence genes, ensuring biosafety. Subsequently, a stable KPN persister model was established using amikacin, with a biphasic killing pattern observed during treatment. At a multiplicity of infection of 10, the phage cocktail eliminated 99.00% of persister cells, while individual phages were less effective. The phage cocktail also inhibited persister-derived biofilm formation, showing improved results when combined with amikacin. This combination significantly reduced capsule polysaccharide production in persisters, weakening the outer membrane barrier. These findings demonstrate that the phage cocktail-amikacin combination effectively targets planktonic cells, persister cells, and biofilms, providing a promising strategy against persisters and recurrent K. pneumoniae infections.
    IMPORTANCE: This study fills the critical gap in understanding how phage cocktails synergize with amikacin against K. pneumoniae persister cells. By constructing a highly specific phage vB_KpnM_NB cocktail, establishing a stable persister model, and performing in vitro bactericidal and biofilm assays, we demonstrate that the cocktail effectively eliminates planktonic cells, persisters, and biofilms. We clarify the core synergistic mechanism: inhibiting capsular polysaccharide synthesis, improving phage adsorption, and disrupting the bacterial outer membrane barrier. These findings provide experimental evidence for the prevention and control of multidrug-resistant and carbapenem-resistant K. pneumoniae persister infections, establishing a safe and effective phage-antibiotic combination therapy. The results are crucial for addressing antibiotic tolerance and controlling chronic, recurrent infections. They hold significant theoretical and translational value for the treatment of refractory infections in clinical settings and offer new insights into the development of novel antimicrobial strategies.
    Keywords:  Klebsiella pneumoniae; biofilm; persister cells; phage cocktail; synergistic effect
    DOI:  https://doi.org/10.1128/aem.01367-26
  28. Front Microbiol. 2026 ;17 1906882
    Evolutionary dynamics and research hotspots of phage applications against Klebsiella pneumoniae infections from the past to the new era.
    Jiawei Zhang, Yanan Liu, Yaru Wang, Wei Zhang, Jianhua Liu, Zhihua Zhang.
       Background: Klebsiella pneumoniae is a critical opportunistic pathogen, with carbapenem-resistant K. pneumoniae and hypervirulent K. pneumoniae posing severe threats to global public health due to escalating antimicrobial resistance. As natural bacterial predators, phages represent a highly promising alternative to conventional antibiotics. The aim of this study was to systematically evaluate the research landscape, collaborative networks, and evolutionary trends of phage applications against Klebsiella pneumoniae infections through bibliometric analysis.
    Methods: Core bibliographic data were retrieved from the Web of Science Core Collection, Scopus, and PubMed databases. Following rigorous literature screening based on predefined inclusion and exclusion criteria, mainstream bibliometric analysis tools, including VOSviewer and CiteSpace, were comprehensively deployed to map and analyze the temporal dynamics of publication outputs, international collaboration networks among countries, institutions, authors, and journals, reference co-citation matrices, and keyword co-occurrence configurations, alongside timeline visualizations and citation burst detection, thereby systematically delineating the evolutionary blueprint of this research domain.
    Results: A total of 1,275 valid original publications were ultimately enrolled. Chronologically, the global annual publication volume exhibited a pronounced exponential growth trajectory (y = 3.4589⋅e 0.2381(x-2007), R 2 = 0.9706). Geographically and structurally, China ranked first globally in research productivity with 242 documents (18.98%), the Chinese Academy of Sciences (49 documents) and investigator Jianqiang Li (30 documents) were identified as the most prolific institution and core author, respectively. Regarding publishing channels, Frontiers in Microbiology dominated in both publication scale (55 documents) and network integration density (TLS = 237). Research hotspot evolution indicated a profound paradigm shift, where contemporary citation bursts are significantly dominated by "phage resistance" (strength = 3.34) and "lytic activity" (strength = 2.77), with both frontiers remaining actively sustained into 2026.
    Conclusion: Over the past two decades, research has expanded exponentially, with the knowledge architecture transitioning from descriptive biological characterization to deep genetic mechanisms and engineering-driven design. Future efforts should prioritize elucidating the molecular mechanisms of phage resistance, optimizing lytic enzyme efficacy, and accelerating multicenter translational interventions to combat multi-drug resistant K. pneumoniae.
    Keywords:  CiteSpace; Klebsiella pneumonia; VOSviewer; bibliometric analysis; phage
    DOI:  https://doi.org/10.3389/fmicb.2026.1906882
  29. J Wound Care. 2026 Sep 02. 35(9): 768-778
    Does teamwork make the dream work? A scoping review of multidisciplinary teams in pressure injury prevention and management.
    Gdiom Gebreheat, Alison Porter-Armstrong.
       OBJECTIVE: To identify, map and synthesise, available contemporary evidence on multidisciplinary team roles and approaches in delivering person-centred prevention and management of pressure injuries (PIs) across the lifespan.
    METHOD: A scoping review was conducted. Searches were undertaken in MEDLINE/PubMed, CINAHL Ultimate, APA PsycInfo, Cochrane Library, PEDro, and Web of Science, alongside grey literature searches and reference screening. Studies published in English between 2016 and 2026 were included if they addressed multidisciplinary team roles in person-centred prevention and management of PIs.
    RESULTS: Eight studies published between 2018 and 2025 were included, with most focusing on adult inpatient populations. Multidisciplinary teams commonly included nurses, wound care specialists, physicians, dietitians, physiotherapists and quality improvement professionals. Nurses held central roles in assessment, prevention implementation, education, coordination and monitoring, while wound care specialists provided leadership and clinical expertise. Multidisciplinary team approaches incorporated staff education, skin care champion programmes, standardised risk assessment, quality surveillance and rapid response systems. Only two studies demonstrated patient and family engagement through education, digital communication and shared care planning. All studies reported reductions in PI incidence or prevalence, supported by leadership engagement, embedded multidisciplinary team structures and continuous quality improvement processes.
    CONCLUSION: Sustainable person-centred prevention and management of PIs require integrated multidisciplinary team approaches that promote shared accountability, clinical expertise and ongoing improvement. Future research should explore the development and support of expanded person-centred multidisciplinary team models across broader age groups and community settings to enhance clinical implementation of PI prevention and management strategies.
    Keywords:  interprofessional collaboration; management; multidisciplinary team; person-centred care; pressure injuries; pressure injury prevention; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2026.0335
  30. Front Cell Infect Microbiol. 2026 ;16 1865385
    16S rRNA sequencing and conventional culture provide complementary information in hospitalized patients with chronic lower-limb wounds.
    Bartosz Molasy, Jarosław Rachuna, Monika Wawszczak-Kasza, Julia Dulębska, Katarzyna Kuszewska, Wioletta Adamus-Białek.
      Chronic lower-limb wounds are polymicrobial and difficult to characterize using conventional culture alone. We compared baseline wound microbiota assessed by 16S rRNA sequencing and conventional culture in 62 hospitalized adults with chronic lower-limb wounds and examined associations with subsequent length of stay. Sequencing detected a mean of 11.62 taxa per sample versus 2.24 by culture, with an overall concordance of 51.35%. In sequencing-based analyses, alpha diversity was not associated with length of stay, whereas beta diversity differed significantly according to hospitalization duration (PERMANOVA, R² = 0.030, p = 0.005), and six genera were associated with length of stay. Conventional culture showed no significant association with length of stay. No significant associations were found between sequencing-derived baseline microbiota and wound thermal parameters or 12-week healing. These findings indicate that 16S rRNA sequencing and conventional culture provide distinct yet complementary views of chronic wound microbiology.
    Keywords:  16S rRNA sequencing; chronic wounds; conventional culture; length of stay; wound healing; wound microbiome
    DOI:  https://doi.org/10.3389/fcimb.2026.1865385
  31. Microbiologyopen. 2026 Oct;15(5): e70394
    Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.
    Selahattin Ünlü.
      Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.
    Keywords:  WHO priority pathogens; antimicrobial resistance; bibliometrics; molecular diagnostics; resistance markers; whole‐genome sequencing
    DOI:  https://doi.org/10.1002/mbo3.70394
  32. Expert Rev Anti Infect Ther. 2026 Sep 03.
    Methicillin resistant staphylococcus aureus treatment and control in neonates: lessons learned - a Vietnam perspective.
    Jennifer Le, Tavin Sayles, Duy Kieu Nguyen, Anh Viet Nguyen, Ha Thu Vu, Nga Thi Bich Nguyen, Dua Thi Nguyen.
       INTRODUCTION: Vietnam bears a substantial burden of methicillin-resistant Staphylococcus aureus (MRSA), yet neonatal data on epidemiology, antimicrobial resistance, treatment, and prevention remain limited and fragmented across regions and healthcare settings.
    AREAS COVERED: This review summarizes MRSA epidemiology, risk factors, treatment, and prevention in neonatal intensive care units (NICUs), identifies key knowledge gaps, and highlights priorities for clinical practice, antimicrobial stewardship, and future research to support more effective management and control strategies. MRSA comprises 73% of S.
    AUREUS: isolates nationally, with notable regional variation. Antibiotic overuse is common, affecting roughly 67.4% of hospitalized patients, and up to 90% of pediatric prescriptions are inappropriate, driving resistance. Vancomycin remains the first-line therapy for severe MRSA infections. Alternative agents - including linezolid, daptomycin, ceftaroline, clindamycin, and adjunctive rifampin - have limited roles, underscoring the importance of local antibiogram-guided therapy.
    EXPERT OPINION: Optimizing vancomycin use through AUC-guided dosing, therapeutic drug monitoring, and de-escalation is critical to balance efficacy and toxicity. Although MRSA remains largely susceptible to vancomycin, the emergence of vancomycin-resistant enterococci (up to 34%) threatens last-line treatment sustainability. Effective strategies to reduce MRSA burden include infection prevention bundles, surveillance cultures, targeted decolonization, and antimicrobial stewardship programs. These interventions must be tailored to Vietnam's healthcare.
    Keywords:  MRSA; antimicrobial resistance; infants; limited-resource country; neonatal intensive care unit; staphylococcus aureus
    DOI:  https://doi.org/10.1080/14787210.2026.2726969
  33. J Multidiscip Healthc. 2026 ;19 631927
    Caregiver Burden Mediates the Association Between Patient Self-Care Behaviors and Psychological Distress in Diabetic Foot Ulcer Care.
    Xiang Chen, Li Tong, Rong Zhang, Youwen Gong, HongLing Zheng.
       Background: Home-based wound care is an important care model for patients with diabetic foot ulcers. In this setting, family caregivers often undertake daily supervision, wound observation, treatment coordination, and care-related decision-making. However, the relationship between patient self-care behaviors and caregiver psychological outcomes remains insufficiently understood.
    Aim: To examine the associations among patient self-care behaviors, caregiver burden, and caregiver psychological distress, and to explore whether caregiver burden mediated the relationship between patient self-care behaviors and caregiver anxiety and depression.
    Methods: A cross-sectional study was conducted among 567 patient-caregiver dyads receiving home-based wound care for diabetic foot ulcers. Patient self-care behaviors were assessed using the Summary of Diabetes Self-Care Activities Scale. Caregiver burden was measured using the Zarit Burden Interview. Caregiver anxiety and depression were assessed using the Self-Rating Anxiety Scale and the Self-Rating Depression Scale. Correlation, multiple regression, and bootstrap mediation analyses were performed.
    Results: The mean patient self-care score was 43.83 ± 15.44, and the mean caregiver burden score was 52.16 ± 18.82. Anxiety and depressive symptoms were identified in 48.0% and 72.5% of caregivers, respectively. Patient self-care behaviors were negatively correlated with caregiver burden, anxiety, and depression, whereas caregiver burden was positively correlated with anxiety and depression. Caregiver burden mediated the association between patient self-care behaviors and caregiver anxiety (indirect effect = -0.222, 95% CI: -0.393 to -0.053) and depression (indirect effect = -0.893, 95% CI: -0.948 to -0.837).
    Conclusion: Better patient self-care behaviors were associated with lower caregiver burden and psychological distress. Caregiver burden may represent a potential pathway linking patient self-care behaviors to caregiver anxiety and depression, although causal inference cannot be made from this cross-sectional study. Home-based diabetic foot ulcer care should integrate patient self-management support with caregiver burden assessment and psychological support.
    Keywords:  anxiety; caregiver burden; depression; diabetic foot ulcer; home-based wound care; mediation analysis; self-care behavior
    DOI:  https://doi.org/10.2147/JMDH.S631927
  34. Chest. 2026 Aug 31. pii: S0012-3692(26)06527-X. [Epub ahead of print]
    The airway microbiome in asthma.
    Hollian Richardson, Jennifer Pollock, Rory Chan, James D Chalmers.
       TOPIC IMPORTANCE: Asthma is a heterogenous airways disease characterized by variable airflow limitation, airway inflammation and bronchial hyperresponsiveness. There is evidence to suggest that the airway microbiome plays an important role in asthma pathophysiology. Most microbiome studies have investigated the bacterial constituents of the microbiome and further studies are needed to investigate the role of the airway virome and mycobiome in asthma.
    REVIEW FINDINGS: Airway microbiome dysbiosis is associated with asthma development, disease severity and inflammatory endotypes. However, it remains unclear whether dysbiosis drives inflammation or is a result of inflammation. Haemophilus and Moraxella alongside rhinovirus and respiratory syncytial virus have been shown to be associated with the development of asthma in children. In established asthma, airway microbiome dysbiosis is associated with severity and risk of exacerbation. Distinct airway microbiome profiles are observed for the different inflammatory endotypes. Asthmatic patients with eosinophilic inflammation have higher microbial diversity similar to healthy individuals while neutrophilic inflammation is associated with reduced microbial diversity, higher bacterial load and a pathogen-dominated microbiome profile suggesting an important role for dysbiosis in asthma that is currently refractory to anti-T2 biologic therapy.
    SUMMARY: To understand the role of the microbiome in asthma, microbiome data must be integrated with other 'omic approaches' such as proteomics. Recent studies have used a multi-omic approach to investigate the microbiome and host interaction as well as identifying asthma endotypes and potential therapeutic targets. Antibiotics, probiotics, monoclonal antibodies, and diet could theoretically be used to therapeutically target the airway and gut microbiome in asthma.
    Keywords:  asthma; microbiome
    DOI:  https://doi.org/10.1016/j.chest.2026.08.032
  35. Health Sci Rep. 2026 Sep;9(9): e73161
    AI-Enhanced System for Diabetic Foot Ulcer Localization and Classification Using Multi-Scale Neural CNN Model.
    Md Nur-A-Alam, Md Anwar Hussen Wadud, Mostofa Kamal Nasir, Khandaker Mohammad Mohi Uddin.
       Background and Aims: Diabetic foot ulcers (DFUs), which heal slowly because of inadequate blood supply, are among the serious infections and chronic foot problems that can result from diabetes mellitus (DM). The primary consequence of DFU, which can result in amputation if left untreated.
    Methods: The paper proposes an intelligent and automated approach for classifying foot images as either healthy or DFU images. At the initial stage, the proposed system presents a novel dataset containing 5500 foot images collected from diverse individuals with healthy and DFU conditions. The preprocessing stage involves three steps: the Region of Interest (ROI) method removes unnecessary portions of the foot images, the RGB images are converted to grayscale, and Non-Local Means (NLM) filtering is applied to reduce noise and remove unwanted information. Two neural feature extractors, ResNet50 and Faster R-CNN, are used to independently extract features from the foot images, and the resulting feature vectors are integrated into a single fused feature. The softmax function of Faster RCNN method classifies DFU or normal image using fused features, and bounding box method regressor function localize the ulcer region from DFU image.
    Results: Compared with relevant state-of-the-art methods, the proposed Faster RCNN-based deep learning approach with feature fusion demonstrates superior performance in DFU recognition, achieving a testing accuracy of 99.85%, specificity of 99.37%, and precision of 99.50%. With a detection accuracy of 98.83%, this fusion-based approach demonstrated competitive performance through the use of a generalization validation mechanism.
    Conclusion: For automated diabetic foot ulcer identification and localization, the suggested fusion-based Faster R-CNN framework shows very accurate and dependable performance. These results point to its significant potential as a helpful clinical decision-making tool for the early identification and treatment of DFU.
    Keywords:  diabetic foot ulcer (DFU); faster region‐convolutional neural network (RCNN); neural feature integration; non‐local means (NLM) filtering method
    DOI:  https://doi.org/10.1002/hsr2.73161
  36. Eur J Microbiol Immunol (Bp). 2026 Sep 04. pii: 1886.2026.00041. [Epub ahead of print]
    Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.
    Umida Nabieva, Dilorom Abdusamatova, Aziz Kubaev, Nigora Turdiyeva, Kamol Komilov.
      Antimicrobial resistance in ESKAPE pathogens is primarily attributed to resistance genes, yet persistent infections despite appropriate therapy implicate immune evasion as an independent driver of treatment failure. Although immune-evasion mechanisms have been extensively characterized in individual pathogens, their shared architecture across the ESKAPE group remains insufficiently integrated. This review synthesizes current evidence to show that phylogenetically diverse ESKAPE pathogens have convergently evolved conserved strategies to evade host immunity under comparable selective pressures. A cross-pathogen immune-evasion framework emerges, encompassing impaired pathogen recognition, complement inhibition, phagocyte dysfunction, immunometabolic reprogramming, biofilm-mediated protection, and persistence-promoting inflammation, together with pathogen-specific virulence mechanisms. These processes intersect with adaptive immune dysfunction and emerging concepts, including quorum-sensing-mediated immunomodulation, trained immunity, and the itaconate-succinate immunometabolic axis, forming an interconnected persistence network rather than isolated virulence traits. This systems-level perspective identifies conserved host-directed therapeutic targets that may complement conventional antimicrobial therapy across species. However, host-directed therapies, immunotherapeutics, and vaccines remain largely preclinical or have shown inconsistent clinical efficacy. Mechanistic evidence is strongest for Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, whereas substantial knowledge gaps persist for Enterococcus faecium, Acinetobacter baumannii, and Enterobacter spp. Overcoming persistent ESKAPE infections will require targeting conserved host-pathogen interactions alongside pathogen-specific antimicrobial resistance mechanisms.
    Keywords:  Convergent immune evasion; ESKAPE pathogens; Host-directed therapy; Immunometabolism (itaconate–succinate axis); trained immunity
    DOI:  https://doi.org/10.1556/1886.2026.00041
  37. J Cyst Fibros. 2026 Sep 03. pii: S1569-1993(26)03721-5. [Epub ahead of print]
    The cystic fibrosis gut microbial dysbiosis index (CF-GMDI): a quantitative measure of gut microbial imbalance in children with cystic fibrosis.
    B L D Uthpala Pushpakumara, Michael J Coffey, Jennifer Hudson, Jessica Halim, Sandra Chuang, Bernadette Prentice, Adam Jaffe, Robert Edwards, Andrew S Day, Mark Oliver, Sarath Ranganathan, Claire Wainwright, Hiran Selvadurai, Josie van Dorst, Chee Y Ooi.
       BACKGROUND: Gut dysbiosis is a hallmark of cystic fibrosis (CF), typically characterised using non-specific diversity metrics and study-specific taxonomic lists, limiting comparability across studies. We aimed to develop a metagenomic, species-level CF Gut Microbial Dysbiosis Index (CF-GMDI) to standardise measurement of gut microbial imbalance in children with CF (cwCF) METHODS: CF-GMDI was derived using stool metagenomic data from the PEARL-CF study (70 cwCF; 67 healthy controls (HC); 0-6 years). Differentially abundant taxa were identified between cwCF and HC using MaAsLin2. The index was calculated as the log10 ratio of the summed relative abundances of taxa enriched in CF vs HC to those depleted in CF vs HC. Reproducibility was assessed in the independent EARTH cohort (56 cwCF; 56 HC; 0-18 years). Responsiveness to therapy was evaluated using publicly available metagenomic data from an Elexacaftor/Tezacaftor/Ivacaftor (ETI) study (39 cwCF; 6-18 years).
    RESULTS: CF-GMDI was significantly higher in cwCF than HC (p < 0.001), inversely correlated with species richness (ρ = -0.74, p < 0.001), and higher in pancreatic-insufficient vs pancreatic-sufficient cwCF in the PEARL-CF cohort (p = 0.01). Key ecological and clinical associations were replicated in the EARTH cohort. In the ETI study, CF-GMDI decreased significantly at 6 and 12 months post-treatment, whereas alpha diversity remained unchanged.
    CONCLUSIONS: CF-GMDI is a CF-associated metric that captures clinically relevant gut microbiome restructuring not detected by standard diversity measures in cwCF (0-18 years). It differentiates disease and pancreatic status and tracks therapeutic modulation, supporting its use as a novel endpoint in CF intervention studies.
    Keywords:  Cystic fibrosis; Dysbiosis; Dysbiosis index; Microbial imbalance; Microbiome
    DOI:  https://doi.org/10.1016/j.jcf.2026.08.007
  38. Pharmacol Ther. 2026 Sep 01. pii: S0163-7258(26)00137-3. [Epub ahead of print] 109110
    Antimicrobial photodynamic therapy across ESKAPE pathogens: Efficacy, limitations, and a pathogen-adapted framework toward clinical translation.
    Angélica R Bravo, Matías Fabián Cuevas, Maríaignacia Rubilar-Huenchuman, Camilo Ortega-Villanueva, Vanessa Bustamante, Iván A González, Renato Burgos-Ravanal, Christian Erick Palavecino.
      Multidrug-resistant (MDR) bacteria belonging to the ESKAPE group-Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-represent some of the most urgent threats to global health. These pathogens are major causes of healthcare-associated infections and are characterized by extensive antibiotic resistance, biofilm formation, persistence phenotypes, and multiple virulence mechanisms that limit the effectiveness of conventional antimicrobial therapies. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising non-antibiotic approach based on the light activation of photosensitizers, leading to the generation of reactive oxygen species (ROS) that induce multi-target oxidative damage. This review evaluates the current evidence supporting aPDT against ESKAPE pathogens and examines the biological and therapeutic factors that influence treatment outcomes. Across ESKAPE pathogens, aPDT frequently achieved clinically relevant antibacterial effects, including reductions of ≥3 log₁₀ CFU under optimized conditions. However, treatment efficacy varied substantially according to bacterial envelope architecture, biofilm organization, and infection accessibility. Gram-positive pathogens generally exhibited higher susceptibility, whereas Gram-negative species-particularly P. aeruginosa-required strategies to overcome outer membrane barriers, biofilm-associated protection, and limited photosensitizer penetration. Beyond direct antimicrobial activity, numerous studies reported biofilm disruption, modulation of virulence-associated pathways, and enhanced susceptibility to conventional antibiotics. Collectively, these findings suggest that aPDT efficacy is determined not only by photosensitizer potency but also by pathogen-specific structural and physiological constraints. Current evidence supports aPDT as a promising adjunctive strategy against MDR ESKAPE pathogens, particularly in localized and accessible infections where effective light delivery can be achieved. The therapeutic performance of aPDT appears to follow a pathogen-dependent gradient shaped by bacterial structure, biofilm complexity, and treatment accessibility. These observations support a pathogen-adapted framework for aPDT development, in which photosensitizer selection, delivery systems, and irradiation strategies are tailored to the biological characteristics of individual pathogens. Future progress will require greater protocol standardization, improved translational models, and well-designed clinical studies to facilitate the integration of aPDT into antimicrobial practice.
    Keywords:  Acinetobacter baumannii; Antibiotic resistance; Enterobacter spp.; Enterococcus faecium; Klebsiella pneumoniae; Photodynamic treatment; Pseudomonas aeruginosa; Staphylococcus aureus
    DOI:  https://doi.org/10.1016/j.pharmthera.2026.109110
  39. Brief Bioinform. 2026 Sep 01. pii: bbag456. [Epub ahead of print]27(5):
    AResKGLM: a graph-grounded language-model framework for interpretable multi-hop antimicrobial resistance reasoning.
    Jie Ren, Ziyi Yang, Wei Liu, Man Tat Alexander Ng.
      Antimicrobial resistance (AMR) threatens microbiology and microbiome bioinformatics because resistance phenotypes are shaped by interactions among genes, mobile genetic elements, and functional environments across microbial communities. Prioritizing resistance determinants requires models that reason across knowledge graphs (KGs) linking genes, proteins, pathways, drugs, and microbial phenotypes. Existing graph-based methods compress this evidence into scalar scores, whereas large language models can produce explanations not grounded in structured evidence. We developed AResKGLM (Antimicrobial Resistance Knowledge Graph Language Model), a graph-grounded language-model framework for interpretable microbial AMR bioinformatics that serializes breadth-first-search-retrieved multi-hop paths and per-entity biomedical descriptions into a structured Context-Path-Question prompt. Llama-3-8B and DeepSeek-R1-7B are adapted with QLoRA to produce binary link predictions and concise reasoning traces. On the KIDs benchmark, AResKGLM (Llama-3-8B) achieved F1 = 0.8482, outperforming KG-BERT (0.7213), NBFNet (0.5260), and ULTRA (0.2541) (paired Wilcoxon $p = 1.2 \times 10^{-7}$). Its advantage increased with reasoning depth: F1 decreased from 0.9197 at 2 hops to 0.8148 at 6 hops, whereas KG-BERT dropped from 0.8110 to 0.6716. Counterfactual path corruption produced an apparent F1 of 0.000, mechanically forced by the probe label assignment; the operative diagnostic is the per-sample flip rate (0.04-0.16), consistent with sensitivity to supplied biological evidence rather than reliance on pretrained priors alone. Cross-species evaluation yielded F1 = 0.81-0.88 with Matthews correlation coefficient (MCC) = 0.35-0.54 on Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Staphylococcus aureus. Temporal ranking of 81 post-2022 gene-drug associations achieved Precision@20 = 100% and AUC-PR = 0.855. AResKGLM offers an interpretable, reproducible framework for multi-hop AMR reasoning, linking candidate prioritization with mechanism-oriented hypothesis generation.
    Keywords:  AMR surveillance; antimicrobial resistance; graph-grounded reasoning; knowledge graph; large language model; microbiome bioinformatics
    DOI:  https://doi.org/10.1093/bib/bbag456
  40. Res Vet Sci. 2026 Aug 26. pii: S0034-5288(26)00321-8. [Epub ahead of print]211 106367
    Outer membrane vesicles in Pseudomonas aeruginosa pathogenesis: a systematic review of virulence dissemination, immune modulation, and antimicrobial resistance, with perspectives for veterinary and one health practice.
    Alfi Sophian.
       BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen recognised for its intrinsic and acquired antibiotic resistance, its capacity to establish chronic infections in cystic fibrosis (CF) airways, and its clinical importance in immunocompromised human and animal hosts. While its extensive secretome has been intensively studied, a mechanistically distinct dissemination strategy has emerged: the constitutive production of outer membrane vesicles (OMVs) that concentrate, protect, and deliver virulence cargo to host cells beyond direct bacterial contact. This systematic review evaluates the molecular mechanisms, biological consequences, antimicrobial resistance implications, and therapeutic prospects associated with OMV-mediated virulence in P. aeruginosa infection, and additionally considers the veterinary and One Health relevance of this evidence base.
    METHODS: A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and EMBASE was conducted from database inception to January 2025 following PRISMA 2020 guidelines. Studies investigating OMV production, cargo characterisation, or biological activity in the context of P. aeruginosa infection were eligible. Risk of bias was assessed using the ToxRTool (in vitro) and SYRCLE tool (in vivo). Inter-rater agreement was quantified by Cohen's kappa (kappa = 0.82).
    RESULTS: Fifty-eight studies (predominantly in vitro and murine models) met the inclusion criteria. P. aeruginosa OMVs (50-250 nm) carry biologically active type III secretion effectors (ExoS, ExoU), elastase (LasB), alkaline protease (AprA), pyocyanin, quorum-sensing autoinducers (3-oxo-C12-HSL), Hcp1, siderophores, and beta-lactamase enzymes including VIM and OXA-type carbapenemases. OMV-packaged beta-lactamases were shown, principally in co-culture experiments, to confer transferable resistance by degrading beta-lactam antibiotics in the extracellular milieu, shielding susceptible bystander bacteria. OMVs drive biofilm maturation, suppress CF airway innate immunity, and induce TLR4-mediated hyperinflammation. OMV output was consistently increased under antibiotic selection pressure, in the CF mucus environment, and during quorum-sensing activation, although the magnitude of increase varied considerably across experimental conditions and should be interpreted qualitatively rather than as directly comparable pooled estimates. Therapeutic strategies targeting OMV biogenesis, cargo neutralisation, and OMV-based vaccine platforms are evaluated, and remain at a predominantly preclinical stage of development.
    CONCLUSIONS: P. aeruginosa OMVs constitute a versatile virulence amplification platform that contributes to tissue destruction, immune evasion, biofilm consolidation, and antibiotic resistance dissemination. Disrupting this multi-functional delivery system represents a promising, though still largely preclinical, antibiotic-independent therapeutic direction for managing refractory P. aeruginosa infections, particularly in CF and critical care settings. Extension of this evidence base to animal-associated P. aeruginosa infections and One Health surveillance is identified as an important priority for future research.
    Keywords:  Antibiotic resistance; Biofilm; Carbapenem resistance; Cystic fibrosis; Elastase; Immune evasion; Outer membrane vesicles; Pseudomonas aeruginosa; Quorum sensing; Type III secretion; Virulence dissemination
    DOI:  https://doi.org/10.1016/j.rvsc.2026.106367
  41. Malays J Pathol. 2026 Aug;48(2): 241-255
    The oral microbiome and dental health during pregnancy: Impact on maternal and foetal health outcomes.
    S W Pan, K K Wong, Q W Lim, E Soo, F C Cheah.
      Hormonal and immune system changes during pregnancy may disrupt the resident oral microbiota causing dysbiosis that may render these women prone to gum health disease, such as gingivitis and periodontitis. This may in turn lead to systemic disorders, such as maternal gestational diabetes mellitus and hypertension, preterm birth, and low birth weight infants. Emerging evidence has associated dysbiosis of the oral microbiota during pregnancy with an imbalance and a preponderance of pathogenic bacteria such as Porphyromonas gingivalis and Fusobacterium nucleatum that may cause both placental and systemic inflammation. To mitigate the consequential adverse effects originating from poor oral health, some strategies have been proposed which include the use of probiotics, antimicrobial agents, laser therapy, and nanotechnology aimed at regulating a healthier oral microbiota to promote better overall health and pregnancy outcomes. This paper also highlights the importance of routine maternal oral health examination and management as a crucial inclusive component of antenatal care, which could positively impact on both the maternal and neonatal health outcomes. Advances and further research in this area will unravel the molecular mechanisms underlying the oral dysbiosis, systemic interactions and the fundamental basis for newer therapies to curb oral health related disorders in pregnancy.
  42. Caspian J Intern Med. 2026 ;17(2): 278-301
    Collagen-based dressings for diabetic foot ulcers: A systematic review.
    Shakiba Rahimi, Mahsa Hosseingholizade, Nahid Hashemi-Madani, Zahra Emami, Mohammad E Khamseh, Zahra Nadia Sharifi.
       Background: To evaluate the efficacy and safety of collagen-based dressings in the management of diabetic foot ulcers (DFUs), compared to standard wound care (SWC), human amniotic membrane allografts (hAMA), and decellularized extracellular matrix (dECM) products.
    Methods: A systematic review of randomized controlled trials (RCTs) and cohort studies published between December 2013 and March 2025 was conducted using PubMed, Scopus, and Web of Science. Eligible studies assessed collagen-based dressings for DFUs, with primary outcomes including wound area reduction, closure rates, and healing time. Adverse events were considered secondary outcomes. Due to heterogeneity, findings were narratively synthesized by dressing type.
    Results: Twenty-two studies (15 RCTs, 7 cohort studies) were included. Collagen-based dressings consistently outperformed SWC, achieving greater wound reduction (54.5--88.2%), higher closure rates (22.2--82.4%), and shorter healing times (21--83.5 days), with no serious treatment-related adverse events. Helicoll showed superior performance (wound reduction: 84--86.5%; closure: 50--71.4%). Comparisons with hAMA and dECM yielded mixed and heterogeneous results, without consistent evidence of superiority. RCTs favored hAMA over Apligraf, while some real-world studies reported the opposite. Findings on collagen/ORC/silver dressings versus dECM were also inconsistent.
    Conclusions: Collagen-based dressings are safe and effective for improving DFU healing when compared with standard wound care. However, current evidence is insufficient and heterogeneous to establish superiority over other advanced biologic therapies. Further head-to-head randomized trials are warranted.
    Keywords:  Collagen-based dressings; Decellularized extracellular matrix; Diabetic foot ulcer; Human amniotic membrane; Standard wound care; Wound healing
    DOI:  https://doi.org/10.22088/cjim.17.2.278
  43. Front Microbiol. 2026 ;17 1957108
    Editorial: Innovative biologics in the battle against bacterial pathogens: disrupting pathogenesis with precision.
    Valeria Szijarto, Gabor Nagy, Adriana Badarau, Christine Tkaczyk.
      
    Keywords:  AMR (antimicrobial resistance); bacterial infection; bacteriophage; biologics; monoclonal antibody; vaccine
    DOI:  https://doi.org/10.3389/fmicb.2026.1957108
  44. Pediatr Pulmonol. 2026 Sep;61(9): e71826
    CFTR Modulator Therapy and Aerobic Fitness Changes in Aerobic Fitness Following Initiation of CFTR Modulator Therapy: A Systematic Review and Meta-Analysis.
    Ingrid Silveira de Almeida, Fernanda Maria Vendrusculo, Mariana Severo da Costa, Márcio Vinícius Fagundes Donadio.
       INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to relevant clinical advances in people with cystic fibrosis (pwCF). However, its effects on aerobic fitness are unclear.
    OBJECTIVE: To evaluate the effects of CFTR modulator therapy on aerobic fitness in pwCF through a systematic review and meta-analysis.
    METHODS: This systematic review (CRD420251066602) was conducted by searching major databases without date or language restrictions. Analytical studies evaluating cardiopulmonary exercise testing outcomes before and after CFTR modulator therapy were included. The primary outcome was peak oxygen uptake (peak VO2). Secondary outcomes included peak VO2 (% predicted), VO2 at the first ventilatory threshold (VT1), breathing reserve, workload, forced expiratory volume in one second (FEV1), and body mass index. Meta-analyses were performed using a random-effects model with heterogeneity assessed by the I2 statistic, and sensitivity analyses conducted.
    RESULTS: Thirteen studies (n = 578 participants) were included, of which 11 were eligible for meta-analysis. The meta-analysis did not identify a significant improvement in peak VO2 (mL·kg-1·min-1) after CFTR modulator use (MD = -0.22; 95% CI: -2.10 to 1.65; p = 0.82). For submaximal outcomes, after sensitivity analysis, VO2 at VT1 was significantly lower in the post-intervention period (MD = -1.85; 95% CI: -2.61 to -1.10; p < 0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI: 2.15 to 13.73; p = 0.007), and workload also increased significantly (MD = 15.39; 95% CI: 2.20 to 28.58; p = 0.02).
    CONCLUSION: CFTR modulator therapy is not consistently associated with improvements in aerobic fitness, as assessed by peak VO2, although it appears to variably influence outcomes related to ventilatory response and exercise performance.
    Keywords:  CFTR modulator therapy, cardiopulmonary exercise testing; aerobic fitness; cystic fibrosis; oxygen consumption
    DOI:  https://doi.org/10.1002/ppul.71826
  45. mSphere. 2026 Sep 03. e0049426
    Uncovering the mechanism of action of a historical antimicrobial against S. aureus and A. baumannii.
    Oluwatosin Qawiyy Orababa, Jessica Furner-Pardoe, Alexander Gale, Blessing Anonye, Joe Ratcliff, Natasha Reddy, Ramón Garcia Maset, Niamh E Harrington, Shajini Subhaskaran, Séamus Holden, Stephen P Diggle, Christophe Corre, Freya Harrison.
      Natural products have provided most of our modern pharmacopeia, serving as active molecules or scaffolds for active molecules. Their use in drug development is often inspired by their traditional or historical medical use. For many decades, this discovery pipeline has focused on identifying a single molecule responsible for much of the biological activity of a "raw" natural product preparation (e.g., a whole-plant extract) and scoping this molecule for clinical potential. However, it is increasingly realized that historical/traditional remedies with significant biological activity may owe this activity to the combined action of multiple molecules. Concomitantly, microbiologists increasingly argue that effectively fighting antimicrobial-resistant infections will rely on combination therapies that combine multiple antimicrobials and/or adjuvant molecules. We previously reconstructed a complex historical remedy, Bald's eyesalve. Our reconstruction of this remedy had strong antibiofilm activity, which relied on the presence of multiple ingredients. Here, we report that Bald's eyesalve has multiple antibacterial effects on exemplar gram-positive (Staphylococcus aureus) and gram-negative (Acinetobacter baumannii) pathogens. Bald's eyesalve disrupts bacterial membrane integrity; inhibits the expression of genes associated with bacterial adhesins, virulence factors, and efflux pumps in both S. aureus and A. baumannii; inhibits quorum sensing in S. aureus; and causes the downregulation of genes involved in de novo nucleotide biosynthesis in S. aureus. Finally, we show that this multifaceted mechanism of action makes it difficult for S. aureus, A. baumannii, and Pseudomonas aeruginosa to evolve resistance against Bald's eyesalve. Bald's eyesalve could be used to identify a defined cocktail of natural products suitable for preclinical testing as a multi-target antibacterial preparation to which resistance may arise more slowly than current single-molecule antibiotics.IMPORTANCEThe increasing mortality and economic cost of antimicrobial resistance (AMR) have made it one of the biggest threats to global health. Available antibiotics are in short supply due to the slow progress in the discovery of new antibiotics. Hence, there is a need for alternative treatment options against difficult-to-treat infections. We have identified a natural product cocktail based on a historical remedy with broad-spectrum antibacterial activity and a multifaceted mechanism of action. We have shown that there is slower resistance evolution to this cocktail compared to mainline antibiotics, and it could be used as the foundation of an alternative treatment to antibiotics in clinical settings.
    Keywords:  AMR; ancientbiotics; antibiotic mechanisms; antivirulence mechanisms; biofilm; natural products
    DOI:  https://doi.org/10.1128/msphere.00494-26
  46. J Med Microbiol. 2026 Sep;75(9):
    Tetracyclines, a timely resurgence or doomed to fail again?
    Samuel Fenn, Dimitra Panagiotopoulou, Kim R Hardie.
      Tetracyclines are bacteriostatic antimicrobials used in the treatment of both bacterial and protozoan pathogens. They abolish protein synthesis by binding to the 16S rRNA, blocking aminoacyl-tRNA access and preventing polypeptide elongation. Tetracyclines are polyketide antimicrobials, with members of this drug family (doxycycline, minocycline and tigecycline) on the World Health Organization (WHO) list of essential medicines. Bacterial resistance to this antimicrobial family is widespread and arises via multiple mechanisms. The most common of these resistance mechanisms are tetracycline efflux, ribosomal protection proteins and the newly emerging tetracycline destructases (TDases). The rise of resistance has limited the clinical use of first- and second-generation tetracyclines; however, third-generation tetracyclines are now reserved as antimicrobials of last resort for complicated bacterial infections. However, genetically mobile TDases have now been identified in opportunistic pathogens, with this mechanism of resistance capable of inactivating third-generation tetracyclines. This presents the question, are third-generation tetracyclines doomed to fail in the same manner as first-generation tetracyclines?
    Keywords:  AMR; antibiotic; antimicrobial resistance; tetracycline
    DOI:  https://doi.org/10.1099/jmm.0.002197
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