bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–06–07
53 papers selected by
Luca Bolliger, lxBio



  1. Trends Microbiol. 2026 Jun 04. pii: S0966-842X(26)00134-4. [Epub ahead of print]
      Phage therapy often fails when bacteria evolve resistance. We argue that phage selection should begin with receptors whose modification imposes predictable costs, turning resistance into reduced virulence, antibiotic resensitization, or other exploitable trade-offs. Receptor-constrained evolutionary traps offer a framework for designing phages that steer-not merely suppress-bacterial evolution effectively.
    Keywords:  evolutionary steering; evolutionary traps; phage resistance; phage therapy; receptor constraint
    DOI:  https://doi.org/10.1016/j.tim.2026.05.011
  2. Virol J. 2026 Jun 02. pii: 143. [Epub ahead of print]23(1):
       BACKGROUND: Enterococcus faecium and Enterococcus faecalis are opportunistic pathogens that form an increasing concern for hospital-acquired infections due to their natural and acquired antimicrobial resistance (AMR). Although phage therapy has gained global interest as a response to emerging AMR, Enterococcus remains an understudied target for phage therapy. In this context, we aimed to isolate Enterococcus-specific phages and study their in vitro infection efficacy when combined into cocktails, in the presence of antibiotics and human serum and against bacterial biofilms.
    RESULTS: We isolated one E. faecium-phage fHoEfm07, that did not resemble any known phage genera and four E. faecalis-phages belonging to Saphexavirus (fHoEfa01 and fHoEfa06) and Efquatrovirus (fHoEfa03 and fHoEfa04) genera. The phages from the genus Saphexavirus and fHoEfm07 were suitable for therapeutic applications based on their genome characterization; however, the phages belonging to the Efquatrovirus genus contained a potential AMR-related gene. In vitro studies indicated that interactions between phages, antibiotics, and human serum depended on the specific phage-host pairing or antibiotic concentration. Moreover, only phage fHoEfa03 reduced the biofilm masses after 3 h and 24 h phage treatment.
    CONCLUSIONS: This study provides valuable insights into the potential of Enterococcus phages in conditions mimicking phage therapy. The characterization of novel phages, assessment of their therapeutic suitability, and exploration of synergistic treatment strategies contribute to the foundational knowledge required to advance phage therapy.
    DOI:  https://doi.org/10.1186/s12985-026-03147-9
  3. Pharmaceut Med. 2026 Jun 04.
      Bacteriophages (phages) are viruses that selectively kill bacteria and offer a promising option to address the growing global pandemic of antimicrobial-resistant infections. However, phage therapy does not easily align with traditional regulatory pathways designed for fixed-composition chemical drugs or biologics with fixed non-evolving compositions. Globally, alternative models such as personalised pharmacy-based formulations (known as magistral preparations), compassionate use provisions and flexible licensing have emerged to accommodate the biological complexity and personalised nature of phage-based therapeutics. Australia is well positioned to take a leadership role and consider a regulatory sandbox approach to the therapeutic use of phages that balances innovation with safety. Being time limited, this controlled framework would allow regulators and innovators to test new approaches under provisional rules and inform potential reforms. A sandbox should include strict participation criteria, and lead to the development of regulatory-ready biobanks of well-characterised phages, accelerating clinical access and manufacturing capacity. This model is a pragmatic and proactive approach that would enable safe scalable phage therapy in response to rising antimicrobial resistance threats.
    DOI:  https://doi.org/10.1007/s40290-026-00614-0
  4. Database (Oxford). 2026 Jan 15. pii: baag033. [Epub ahead of print]2026
      As biology becomes increasingly data-driven, so does the field of phage lysins, enzymes that degrade bacterial cell walls and offer promising alternatives to traditional antibiotics. Five years ago, we introduced PhaLP, a centralized resource for Phage Lytic Protein sequences and associated metadata to support global research efforts. Here, we present PhaLP 2.0, an enhanced database designed to address key challenges in computational lysin research by integrating newly identified lysins from thousands of metagenomes. To expand the known diversity of lysins beyond that of cultured phages, we developed SUBLYME, a protein-embedding-based machine-learning Software designed to Uncover and classify Bacteriophage Lysins from Metagenomic datasets. Using embeddings derived from the well-curated sequences of the original PhaLP database, we trained support vector machines to distinguish lysins from non-lysins in viromes and classify them as endolysins or virion-associated lysins. The models achieved an average F1 score of 98% on held-out clusters. SUBLYME enabled the discovery of 743 000 new lysin sequences from EnVhogDB, a virome-derived protein database, increasing the number of known lysin clusters 40-fold, from 1000 to 40 000. SUBLYME and PhaLP 2.0 are accessible online at https://github.com/Rousseau-Team/sublyme and https://phalp.ugent.be, respectively. Together, these advances establish PhaLP 2.0 as a comprehensive and scalable portal for lysin discovery, classification, and sequence analysis, paving the way for future antibacterial applications and evolutionary insights.
    DOI:  https://doi.org/10.1093/database/baag033
  5. Arch Microbiol. 2026 Jun 06. pii: 426. [Epub ahead of print]208(8):
      Quorum sensing (QS) in Salmonella enterica serovar Typhi (S. Typhi) is a cell-cell communication process mediated by molecules like Autoinducer-2 (AI-2). The production and detection of these molecules are population density-dependent, regulating behaviours essential to virulence and survival. Since the QS stage lies between the initial planktonic stage and the formation of a stable, persistent biofilm, it allows the pathogen to survive and become more virulent. Eradication of S. Typhi requires investigation using effective therapeutic agents, such as biologically-derived therapeutics. Conventional antibiotics have significant limitations when used against S. Typhi. Their efficacy is often hampered by different resistance problems, and they can cause various clinical complications related to their chemical and physical properties. The prolonged use of these drugs can cause host toxicity and may fail to eradicate the pathogen. The persistence of biofilms and the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains have rendered many existing drugs ineffective. Thus, targeting bacterial communication by simply disrupting its signalling mechanism, i.e., QS, might be a better approach for therapeutic development against biofilms. This review aims to critically evaluate current QS inhibitors (QSIs) and, more importantly, to explore the potential of developing bioorganic compounds from natural and biological sources as effective quorum quenching (QQ) agents.
    Keywords:  AMPs; Autoinducers; Phage therapy; Postbiotics; QSIs
    DOI:  https://doi.org/10.1007/s00203-026-04971-x
  6. Infection. 2026 Jun 01.
      Non-tuberculous mycobacteria (NTM) can present a serious clinical threat due to their resistance to conventional antibiotics and their ability to cause persistent infections. As antimicrobial resistance (AMR) represents one of the most significant global health threats, mycobacteriophages (MPs)-viruses that specifically target mycobacterial species-are emerging as a promising therapeutic addition or alternative. This review explores the biological characteristics, therapeutic mechanisms, and clinical potential of MPs, with a primary focus on their use against NTM infections. Based on data from in vitro studies, animal models, and human compassionate-use cases, we highlight the mycobactericidal efficacy of MPs as well as their potential to complement antibiotic treatment regimens. However, there are key challenges that need to be addressed to implement MPs as therapeutics-such as limited host range, immune response interference, MP resistance, and intracellular delivery barriers. The implementation of MP banks, standardized regulatory protocols, and approved clinical trials is highly essential for MP therapy to transition smoothly into the healthcare sectors. By carrying out coordinated scientific, regulatory, and clinical efforts, MP-based therapy holds a promising potential in combating antibiotic-resistant NTM infections.
    Keywords:  Bacteriophages; Mycobacteriophages; NTM; Non-tuberculous mycobacteria; Phage therapy; Phages
    DOI:  https://doi.org/10.1007/s15010-026-02818-7
  7. Front Microbiol. 2026 ;17 1846582
      The escalating global crisis of bacterial antimicrobial resistance (AMR) has significantly limited the clinical efficacy of quinolone antibiotics, while the use of phages alone suffers from inherent limitations, including a narrow host spectrum and the propensity to rapidly induce phage resistance. Consequently, combined antimicrobial therapy, defined as phage-antibiotic synergy (PAS), has emerged as a pivotal direction to address the challenges. The specific objectives of this review are to systematically dissect the bidirectional synergistic and antagonistic interactions between quinolone antibiotics and bacteriophages, define the key regulatory factors governing their combined effects, and establish an evidence-based framework to guide the standardized clinical application of quinolone-based PAS. This paper systematically reviews the mechanisms underlying the synergistic and antagonistic interactions between quinolone antibiotics and bacteriophages. The synergistic effects are manifested across multiple dimensions: bacterial morphological remodeling, activation of temperate phages, disruption of biofilm barriers, potentiation of functional proteins, dual regulation of resistance evolution, and synergy with the host immune system. In contrast, antagonistic effects are primarily triggered by high-concentration antibiotics interfering with phage proliferation, adaptive phenotypic alterations of bacteria, and imbalanced administration strategies. Simultaneously, we summarize standardized clinical optimization strategies, including sequential administration, sub-inhibitory antibiotic concentrations paired with the minimum effective multiplicity of infection (MOI) of phages, rational selection of broad-host-range and highly lytic phages, and individual regimen tailoring to match the specific infectious scenario and host immune status. We further analyze key challenges in the clinical translation of this therapeutic approach and propose future research directions, offering a framework to guide both mechanistic studies and clinical implementation of PAS as a strategy to mitigate antimicrobial resistance.
    Keywords:  antibiotic resistance reversal; antimicrobial resistance; bacterial biofilm; clinical administration strategies; mechanism of action; multidrug-resistant bacteria
    DOI:  https://doi.org/10.3389/fmicb.2026.1846582
  8. Int Dent J. 2026 Jun 01. pii: S0020-6539(26)00243-1. [Epub ahead of print]76(4): 109650
       INTRODUCTION AND AIMS: The polymicrobial synergy and dysbiosis model is increasingly recognized as a key pathogenic factor in periodontitis. Human herpesviruses (HHVs), including EBV, HCMV, and HSV-1, have been linked to periodontitis development. However, current research lacks sufficient evidence to clarify the correlation between HHVs, periodontitis progression, and periodontal microbiota. This study aimed to investigate the association between HHVs in gingival crevicular fluid (GCF) and periodontitis severity, as well as the correlation patterns between viruses and periodontal microbiota.
    METHODS: A total of 339 subjects (64 healthy controls, 275 periodontitis patients) were stratified according to the 2018 periodontitis classification criteria. Viral loads were quantified by quantitative real-time PCR (qPCR), and microbial communities were analysed via high-throughput 16S rRNA sequencing.
    RESULTS: HCMV and EBV loads were significantly positively correlated with clinical parameters including probing depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP) (all P < .001), and their infection status was closely associated with periodontitis staging. HSV-1 showed no significant association with any periodontal indicators (P > .05). In the EBV/HCMV coinfection group, 92.9% of patients were classified as stage II-IV periodontitis, suggesting potential combined viral associations with disease severity. Microbiome analysis revealed significantly higher microbial diversity in the HCMV-H compared to the HCMV-L. HCMV load was positively correlated with known pathogens such as Porphyromonas gingivalis and Tannerella forsythia, as well as novel associated bacteria (eg, Schwartzia succinivorans, Peptostreptococcus stomatis). Functional prediction showed significant enrichment of microbial metabolic pathways in HCMV-H patients, including Helicobacter pylori infection and isoquinoline alkaloid biosynthesis.
    CONCLUSION: HCMV is strongly associated with periodontitis severity and bacterial dysbiosis, while EBV acts as an independent risk factor correlated with periodontitis severity. In contrast, HSV-1 shows no significant association with periodontitis severity. This study provides new evidence for the polymicrobial pathogenesis of periodontitis and highlights virus-bacteria associations as potential therapeutic targets, although further longitudinal studies are needed to establish causality.
    Keywords:  EBV; HCMV; HHVs; HSV-1; Periodontitis
    DOI:  https://doi.org/10.1016/j.identj.2026.109650
  9. Cureus. 2026 May;18(5): e108149
       BACKGROUND: Bacteriophages are ubiquitous viruses that specifically infect and lyse bacterial hosts and have gained increasing attention for applications in biocontrol, phage therapy, food safety, and diagnostics. Efficient isolation of bacteriophages from environmental sources is essential for both research and applied purposes. This study aimed to comparatively evaluate the efficiency of three bacteriophage isolation methods from environmental water samples.
    METHODS: In this comparative methodological study, 96 environmental water samples were collected from four aquatic sites in Tangail, Bangladesh, over a one-year period (January-December 2025), with sampling conducted twice monthly. Six bacteriophages targeting clinically relevant bacterial hosts were assessed using three isolation methods: direct recovery, polyethylene glycol (PEG)-mediated precipitation, and host-based enrichment. Phage recovery efficiency was compared using Chi-square and Fisher's exact tests, and effect sizes were estimated using odds ratios (ORs) with 95% confidence intervals (CIs).
    RESULTS: The average phage recovery rates were 9.38%, 21.35%, and 47.20% for the direct, PEG, and enrichment methods, respectively. A significant difference in recovery proportions was observed among methods (χ² = 224.1, df = 2, p < 0.0001). Pairwise comparisons demonstrated that the enrichment method yielded significantly higher recovery than the PEG method (OR = 3.29, 95% CI: 2.55-4.26, p < 0.0001) and the direct method (OR = 8.65, 95% CI: 6.28-11.97, p < 0.0001).
    CONCLUSIONS: The modified enrichment method significantly improves bacteriophage recovery compared to the direct and PEG-based approaches, particularly for low-abundance phages. This method represents a robust and sensitive strategy for isolating bacteriophages from environmental water samples and may support future applications in phage-based therapeutics, environmental surveillance, and microbial control.
    Keywords:  bacteriophage; direct method; enrichment method; etec; klebsiella pneumoniae; peg method; pseudomonas aeruginosa; salmonella typhimurium; shigella sonnei; vibrio cholerae o1
    DOI:  https://doi.org/10.7759/cureus.108149
  10. bioRxiv. 2026 May 29. pii: 2026.05.27.728049. [Epub ahead of print]
      Accurate quantitation of therapeutic bacteriophages ( phages ) remains a challenge for clinical development. Plaque-based enumeration is the current standard but is laborious, host-dependent, and variable, particularly when distinguishing individual phages in cocktails. Targeted mass spectrometry of virion structural proteins offers an orthogonal, structure-based approach amenable to reproducible and scalable phage quantitation. Here, we describe a targeted proteomic liquid chromatography-tandem mass spectrometry ( LC-MS/MS ) assay for host-independent quantitation of the Pseudomonas aeruginosa podovirus LUZ19. Proteomic characterization was performed on an LTQ Orbitrap XL to assess sequence coverage and select surrogate peptide candidates based on specificity and sensitivity. High-resolution peptide mapping identified multiple structural proteins of LUZ19 and provided 55% sequence coverage for the major head protein (YP_001671977.1). Fifteen peptides were detected and evaluated, from which the tryptic peptide EVAELDGQELAR was selected based on abundance, stability, and chromatographic performance. Quantitative analysis was conducted on a QTRAP 7500+ using optimized multiple reaction monitoring transitions for targeted peptide detection. Back-calculated concentrations met accuracy criteria across a validated range of 0.008 to 80 pg/mL, with bias spanning -8.2 to 8.2%, intra-day precision ranging from 0.5 to 9.8%, and inter-day precision ranging from 6.3 to 9.7%. Peptide concentrations from digested lysate samples were related to phage concentrations determined by double layer agar assay, yielding an estimated three copies of the major head protein per virion.
    Importance: Bacteriophages are the most abundant biological entities on the planet and represent a promising therapeutic class for combating drug-resistant bacterial infections. Realizing the clinical potential of bacteriophage therapy requires analytical methods capable of meeting the standards of modern drug development. Targeted mass spectrometry offers unmatched specificity and resolution for precise quantitation of individual bacteriophages within complex biological samples, a capability that conventional enumeration methods cannot match. Only one prior study has applied mass spectrometry to bacteriophage quantitation, using a well-characterized model bacteriophage at a single concentration without calibration or a validated analytical range. Using Pseudomonas aeruginosa podovirus LUZ19, we present the first targeted mass spectrometry-based bacteriophage quantitation assay developed and validated following FDA bioanalytical guidance. This work establishes a rigorous analytical foundation that moves bacteriophage therapy closer to the standards required for informed dose selection, candidate evaluation, and clinical development.
    DOI:  https://doi.org/10.64898/2026.05.27.728049
  11. Transl Behav Med. 2026 Jan 07. pii: ibag030. [Epub ahead of print]16(1):
       BACKGROUND: Diabetic foot ulcers (DFUs) affect approximately 25% of people with diabetes and are associated with decreased quality of life, high healthcare costs, recurrent wounds, and amputation risk. Standard DFU care emphasizes offloading to promote healing; however, adherence is often poor due to behavioral, psychosocial, and everyday life challenges. These gaps highlight the need for person-centered interventions that support DFU self-management within daily routines.
    PURPOSE: To systematically adapt a Lifestyle Redesign® occupational therapy intervention (LR-OT) for DFU self-management using the ADAPT-ITT framework.
    METHODS: An iterative, stakeholder-engaged adaptation process was conducted across the first seven ADAPT-ITT phases: Assessment, Decision, Administration, Production, Topical Experts, Integration, and Training. Activities included targeted literature synthesis, theater testing with individuals with DFUs and DFU care providers, iterative material development, and expert consultation. Adaptation efforts focused on refining intervention content, delivery, and training supports to DFU-specific care demands while retaining alignment with LR-OT core elements.
    RESULTS: The ADAPT-ITT process yielded an interventionist-ready, DFU-specific LR-OT package, including patient-facing materials, an interventionist resource guide, and a conceptual mapping linking LR-OT theoretical elements to DFU-targeted management activities. Stakeholder input informed coordinated refinements to content, session structure, and delivery to support feasibility within DFU care contexts.
    CONCLUSION: Application of the ADAPT-ITT framework supported a transparent, stakeholder-informed, and reproducible process for adapting an evidence-based occupational therapy intervention for a high-risk and medically complex population. This work illustrates how lifestyle-focused interventions can be systematically adapted for specialty care contexts, with subsequent testing needed to evaluate fidelity and effectiveness.
    CLINICAL TRIAL INFORMATION: #NCT06278935.
    Keywords:  behavior change; chronic disease management; health promotion; intervention adaptation; rehabilitation; stakeholder engagement
    DOI:  https://doi.org/10.1093/tbm/ibag030
  12. Front Immunol. 2026 ;17 1803023
      Chronic wounds represent a major clinical challenge characterized by persistent failure of tissue repair, a phenomenon that cannot be fully explained by infection and inflammation alone. Emerging evidence indicates that wound-associated microbial communities establish stable pathogenic ecosystems that specifically disrupt the proliferative phase of healing, the critical stage responsible for cellular expansion, angiogenesis, and extracellular matrix reconstruction. Here, we propose the conceptual framework of infection-driven proliferative phase impairment (IDPPI), which describes a pathological state in chronic wounds wherein sustained microbial pathogenic activities continuously compromise host regenerative programs. We synthesize current evidence showing that coordinated virulence factor deployment, biofilm persistence, and host immune-metabolic dysregulation converge to induce proliferative arrest. They do so through direct cellular injury, suppression of repair-related signaling pathways, and disruption of cell-cycle control. This integrated pathogenic cascade ultimately locks wounds into a state of low-efficiency or arrested regeneration. Building on this mechanistic framework, we outline a sequential, targeted therapeutic paradigm encompassing three interconnected levels: targeted suppression of virulence and biofilm functions, restoration of immune-metabolic homeostasis within the wound microenvironment, and spatiotemporally controlled promotion of regeneration using responsive biomaterials and cell-free regenerative strategies. Rather than prioritizing non-selective microbial eradication, this approach emphasizes functional disarmament of pathogenic ecosystems and reactivation of host proliferative capacity. Finally, we discuss how advances in spatial multi-omics, biomimetic human-relevant models, artificial intelligence, and real-time sensing technologies can enable dynamic assessment and adaptive intervention, supporting a paradigm shift in chronic wound management from static staging toward feedback-guided (closed-loop), mechanism-informed regenerative medicine. IDPPI is presented as an integrative framework that reorders causality by placing infection-driven disruption of proliferative repair execution as the proximal failure mode.
    Keywords:  antivirulence therapy; biofilm-associated pathogenicity; chronic wounds; immunometabolic dysregulation; infection-driven proliferative phase impairment; precision regeneration; wound microbiome
    DOI:  https://doi.org/10.3389/fimmu.2026.1803023
  13. Aesthetic Plast Surg. 2026 Jun 01.
       BACKGROUND: Wound healing is a complex process involving hemostasis, inflammation, proliferation, and remodeling. Chronic wounds (persisting beyond 6 weeks) and pathological scarring pose significant clinical challenges. These conditions not only impair patient quality of life but also impose heavy economic burdens on healthcare systems. BoNT/A has been widely studied and shows promise in promoting wound healing, reducing pathological scarring, and improving chronic wounds. However, the existing evidence base largely consists of low-level studies, including animal models, case reports, and small clinical trials. While these studies show positive outcomes, their efficacy and long-term safety need to be validated through high-quality large-scale clinical trials. Therefore, it is important to acknowledge the limitations of current evidence and emphasize the need for further research to provide more robust support.
    OBJECTIVE: To comprehensively review the potential roles and underlying mechanisms of BoNT/A in promoting wound healing, preventing pathological scarring, and treating chronic wounds, aiming to provide theoretical insights for clinical applications.
    METHODS: This review synthesizes existing literature on BoNT/A, focusing on its biological mechanisms in wound healing, including effects on inflammation, angiogenesis, fibroblast activity, and extracellular matrix (ECM) regulation. It also summarizes clinical evidence and combination therapies involving BoNT/A for adverse wound outcomes. A literature search was conducted in PubMed, Embase, and Web of Science using the terms "botulinum toxin A", "wound healing", "scar", and "chronic wounds". Publications from the past ten years were prioritized, with earlier landmark studies included when relevant. Both preclinical and clinical evidence was considered to provide a comprehensive overview.
    RESULTS: BoNT/A exerts multifaceted effects: it inhibits inflammatory responses by reducing mediators like IL-6 and substance P; promotes angiogenesis via HIF-1α/VEGF and nitric oxide pathways; modulates fibroblast activity by suppressing TGF-β1/Smad and ERK signaling to reduce abnormal collagen deposition; and improves wound microenvironment by reducing tension and regulating sweat/sebum secretion. Combination therapies (e.g., with steroids, lasers, or hyaluronic acid) enhance efficacy in scarring and chronic wound treatment.
    CONCLUSION: BoNT/A has been widely studied and most reports suggest a favorable short-term safety profile; however, current evidence is predominantly low-level (animal studies, case reports, small series) and all wound-care uses remain off-label, underscoring the need for adequately powered randomized trials and long-term safety data.
    LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
    Keywords:  Botulinum toxin A; Chronic wounds; Scarring mechanism; Wound healing
    DOI:  https://doi.org/10.1007/s00266-026-05866-4
  14. Front Dent Med. 2026 ;7 1853472
      
    Keywords:  biomarkers; cardiovascular diseases; diabetes mellitus; microbiota; periodontitis; systemic inflammation
    DOI:  https://doi.org/10.3389/fdmed.2026.1853472
  15. Curr Opin Biotechnol. 2026 Jun 04. pii: S0958-1669(26)00092-3. [Epub ahead of print]100 103527
      Nanoparticles are now central to many drug and vaccine delivery strategies, but most require reformulation for each application. Bacteriophage‑derived nanoparticles offer a genetically encoded, structurally defined, and modular alternative. This review organizes recent advances along three tunable axes - scaffold, surface, and cargo - and highlights hybrid phage-polymer/lipid/inorganic constructs that expand stability, targeting, and loading. We survey applications from multivalent vaccines and oversized gene transfer to precision microbiome editing, and outline translational hurdles. Phage-derived products are approaching translation, with virus-like particle-based vaccines and CRISPR-enhanced antimicrobial phages in clinical trials. Finally, we preview emerging opportunities, including AI‑guided capsid and receptor‑binding protein design, cell‑free phage synthesis, and standardized 'reference' phage chassis that can be combined with traditional nanoparticles, positioning phage nanoparticles as reusable, plug-and-play nanomedicines.
    DOI:  https://doi.org/10.1016/j.copbio.2026.103527
  16. bioRxiv. 2026 May 25. pii: 2026.05.24.727406. [Epub ahead of print]
      Bacteriophages (phages) play essential roles in microbial systems, yet most phage proteins remain poorly characterised. Protein tertiary and quaternary structure information contributes valuable information about protein function. As many phage proteins function as homooligomers, complexes that consist of multiple identical subunits, there is great interest in computationally predicting their configurations. Here we present a computational framework, the Phage Homomer Level Estimate and Generation Method (PHLEGM) for inferring homooligomeric states directly from the protein sequence by combining AlphaFold-Multimer modelling with inter-subunit interface quality assessment. We proceeded to experimentally validate two out of nine predicted homooligomers using size exclusion chromatography and complementary hydrodynamic techniques. These efforts confirmed our predictions for a dimer and a trimer, highlighting the value of experimentally benchmarked computational predictions and showing the challenges of heterologous phage protein production. Applied to >22,000 phage protein sequences in the PHROGs database, our approach revealed extensive diversity in phage homooligomeric protein complexes. Benchmarking against protein language model-based predictors on a curated reference set of known phage homooligomers demonstrated superior accuracy of our structure-based method, achieving robust performance in classifying protein homooligomeric states, with the highest accuracy observed for trimers and higher-order complexes. These results highlight the value of computational predictions to decipher the complexities of the vast viral sequence space. All predicted complex structures and functional inferences are made publicly available to support structural and functional studies of phage proteins.
    DOI:  https://doi.org/10.64898/2026.05.24.727406
  17. Adv Appl Microbiol. 2026 ;pii: S0065-2164(26)00002-X. [Epub ahead of print]133 113-140
      Rapidly growing nontuberculous mycobacteria (NTM) are emerging pathogens that are well-known entities behind pulmonary, extra-pulmonary, cutaneous, subcutaneous, as well as systemic and disseminated infections. Mycobacterium fortuitum is an important human pathogenic NTM. It is a routine nosocomial contaminant capable of forming resilient biofilms that enhance its resistance to antibiotics and disinfectants and contribute to persistent healthcare-associated infections. Moreover, varying symptoms of M. fortuitum infections, long duration therapeutics, and lack of a standardized drug regimen underscores medical significance of the pathogen. Limited knowledge regarding M. fortuitum pathogenesis, however, entices research investigating M. fortuitum planktonic as well as the biofilm phenotype. The review article aims to gather data about the prevalence and clinical significance of NTM in general, with special emphasis on M. fortuitum. It further delves into the biofilm aspect of the pathogen and examines current therapeutic strategies against NTM infections and diseases. Emerging horizons in NTM therapeutics, including repurposing antitubercular drugs, bacteriophage therapy, photodynamic therapy, and advancements in molecular diagnostic techniques are being explored to combat NTM infections. In addition, innovative treatments specifically targeting NTM biofilms, such as combination therapies, liposomal formulations, thiopeptide antibiotics, monoclonal antibodies, and inhibitors of the DosRS system, are under investigation. The concluding section of the article emphasizes the necessity for future research to delve into molecular mechanisms underlying biofilm formation and maintenance, develop targeted therapies, and refine diagnostic tools to effectively manage and treat NTM infections. Collectively, the information will be helpful to the researchers working on strategies and treatments to combat NTM infections.
    Keywords:  Anti-NTM drugs; Biofilm; Mycobacterium fortuitum; Nontuberculous mycobacteria (NTM); Pathogenesis; Pulmonary disease
    DOI:  https://doi.org/10.1016/bs.aambs.2026.04.002
  18. Probiotics Antimicrob Proteins. 2026 Jun 01.
      Periodontitis is a chronic inflammatory disease caused by dysbiosis of the periodontal microbiome, threatening both oral and systemic health. Current prevention and treatment strategies for periodontitis mainly rely on mechanical therapy, with antibiotics used as supplements. However, limitations of mechanical therapy and increasing antibiotic resistance have prompted the exploration of new adjunctive strategies. Probiotic therapy, particularly Lacticaseibacillus rhamnosus (L. rhamnosus), formerly known as Lactobacillus rhamnosus, has emerged as a promising approach due to its ability to modulate periodontal microecology. L. rhamnosus exerts therapeutic effects by inhibiting pathogens, modulating immune responses, and promoting tissue repair. L. rhamnosus has been applied in various forms for the adjuvant treatment of periodontitis and numerous clinical trials have confirmed its safety and effectiveness, indicating broad potential for application. Nevertheless, current clinical studies still face challenges such as unclear strain-specific effects and a lack of standardized administration protocols. Future research should investigate the mechanisms of different strains and evaluate targeted interventions in diverse patient populations to advance the clinical use of probiotic therapies.
    Keywords:   Lacticaseibacillus rhamnosus ; Immunoregulation; Periodontitis; Probiotics
    DOI:  https://doi.org/10.1007/s12602-026-11074-y
  19. Eng Microbiol. 2026 Jun;6(2): 100277
      Infections caused by bacteria pose a risk to humanity as drugs become increasingly ineffective as resistance to bacterial strains emerge along with biofilm and persister formation. This review critically evaluates host defense peptides, rational design strategies that have guided next-generation antimicrobial peptide (AMP) discovery, and their current limitations. We also highlight optimization approaches including sequence engineering and chemical modification, synergistic combinations of antibiotics or adjuvants, and nanoscale delivery platforms that enhance stability, targeted delivery, and biofilm penetration. We also discuss the key chemical properties, delivery kinetics, and stimuli-responsive drug delivery for antibacterial and antibiofilm actions as well as the toxic effects of organic- and inorganic-based AMP delivery platforms. This underlines the importance of diverse modification techniques and artificial intelligence (AI)-assisted designs to improve the antibacterial activity, stability, and biocompatibility of AMPs. This study examines the latest advances in the combination of AMPs with drug delivery systems to improve clinical outcomes. Finally, the review discusses the clinical status, research gaps, current obstacles, and prospects of AMPs in antimicrobial resistance (AMR) therapy, offering key findings for the development of innovative AMPs with significant antibacterial activity, stability, and safety for AMR treatment.
    Keywords:  Antimicrobial peptides; Bacterial infections; Drug delivery
    DOI:  https://doi.org/10.1016/j.engmic.2026.100277
  20. Synth Syst Biotechnol. 2026 Dec;14 368-377
      Bacteriophage therapy emerges as a pivotal alternative in the ongoing battle against antibiotic-resistant bacteria. Employing probiotic bacteria as hosts for bacteriophage production bestows several notable advantages compared to traditional pathogenic hosts. These advantages encompass an enhanced safety profile, streamlined downstream processing, and greater regulatory acceptance. In this study, we engineered Escherichia coli Nissle 1917 (EcN), a non-pathogenic probiotic strain, to serve as a safe chassis host for efficient coliphage production. EcN is resistant to T1, T3, T5, and T7 phages and the T4 phage can only infect it at high titers. By eliminating all known phage defense systems in the genome, we constructed the EcN-9 strain that is susceptible to T3 and T7 phages. The infection efficiency of the T4 phage on the EcN-9 strain was 1000 times higher than that on the EcN-WT strain. Introduction of the appropriate FhuA receptor in EcN-9 rendered it susceptible to T1 and T5 phages. Optimizing the expression levels of FhuA led to a remarkable enhancement in the efficiency of plating, with increases of 3872-fold and 2593-fold for T1 and T5, respectively. Building upon this foundation, we further refined the phage production process by developing a fed-batch fermentation strategy, which not only substantially reduced the multiplicity of infection for inoculation to 0.1, but also resulted in high phage titers, reaching 4.47 × 1010 PFU mL-1 for T1, 9.21 × 1010 PFU mL-1 for T4, and 7.22 × 1010 PFU mL-1 for T5. This study provides a strategic framework for adapting preferred bacterial host systems to produce target phages.
    Keywords:  Phage defense system; Phage production; Phage receptor; Phage therapy; Probiotic bacteria
    DOI:  https://doi.org/10.1016/j.synbio.2026.04.030
  21. Front Microbiol. 2026 ;17 1825173
      This study provides the first shotgun metagenomic characterization of infected diabetic foot ulcers (DFUs) from North Africa. We analyzed two independent datasets with distinct roles: 25 non-infected US DFUs (PRJNA506988) served as an ecological reference cohort to characterize depth-stratified microbial community patterns and pre-infection ARG ecology; 15 infected Libyan DFUs constituted the primary characterization cohort. Metagenomic sequencing, taxonomic classification, resistome and virulome profiling, and metagenome-assembled genome (MAG) reconstruction were performed. In the US reference cohort, depth-dependent community shifts were documented: Fusobacteriota predominated in deeper ulcers, while Staphylococcaceae and Pseudomonadaceae were enriched in superficial wounds. Eighty ARGs were detected across depth groups, including mecA and the mexAB-oprM efflux system, in clinically non-infected wounds. In the Libyan cohort, four major opportunistic pathogens were identified: Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, and Corynebacterium striatum. From sample M13, a high-quality P. aeruginosa MAG (99.68% completeness, 0.89% contamination) was reconstructed, classified as ST664 and carrying 220 virulence factors, 60 antibiotic resistance genes (all confirmed by RGI v6.0.2), and 213 mobile genetic elements. These findings represent the first genomic evidence of ST664 in a North African DFU and underscore the need for metagenomics-guided antimicrobial stewardship in chronic wound management.
    Keywords:  Pseudomonas aeruginosa; antimicrobial resistance; biofilm; diabetic foot ulcers; microbiome; resistome; shotgun metagenomics; wound infection
    DOI:  https://doi.org/10.3389/fmicb.2026.1825173
  22. APMIS. 2026 Jun;134(6): e70228
      The spread of multidrug-resistant microorganisms remains a major global challenge that continues to worsen. Modern military conflicts intensify this problem by forcing healthcare systems to manage large numbers of patients with complex, heavily contaminated injuries in resource-limited settings. This can disrupt infection prevention and control and promote the emergence and spread of resistant pathogens. In this context, antiseptics are essential in combat wound management and should be used throughout patient care, from first aid to rehabilitation. Among them, active chlorine compounds deserve special attention because of their broad-spectrum, rapid microbicidal action, minimal risk of resistance development, good tolerability, and affordability. This review summarizes recent advances in their use for wounds of various origins. Active chlorine preparations are highly effective against microorganisms that commonly complicate acute and chronic wounds, including multidrug-resistant and biofilm-forming pathogens. In addition, their anti-inflammatory, reparative, and immunomodulatory properties may accelerate healing through multiple mechanisms while maintaining low toxicity. The broad range of formulations, from traditional hypochlorous acid solutions to polymers with N-Cl moieties and wearable electrochemical dressings, supports use in both field and hospital settings. Together, these features make active chlorine products promising non-antibiotic tools for modern wound infection control, particularly in military medicine.
    Keywords:  active chlorine; antimicrobial resistance; antiseptics; combat‐associated injuries; wound care
    DOI:  https://doi.org/10.1111/apm.70228
  23. Microb Pathog. 2026 Jun 01. pii: S0882-4010(26)00327-X. [Epub ahead of print] 108601
      Invasive fungal infections in intensive care units are a serious concern, especially when they are associated with biofilm formation. These infections often lead to high mortality because biofilms make the fungi more resistant to antifungal drugs and harder for the immune system to clear. Pathogens such as Candida auris, Candida albicans, and Aspergillus fumigatus are particularly problematic, as they are known to develop multidrug resistance and cause persistent infections in critically ill patients. These biofilms often show a much higher tolerance to standard antifungal drugs and can escape the host body's immune defenses. This makes the infections they cause more persistent and very difficult to treat in clinical practice. Antifungal peptides (AFPs), whether derived from natural host-defense molecules or designed through rational engineering, are emerging as promising options for tackling fungal biofilms. They act through several mechanisms, such as disrupting the fungal cell membrane, blocking early adhesion and morphogenesis, and weakening the extracellular matrix. Importantly, they may also work in synergy with existing antifungal drugs, making treatment more effective. Recent progress in peptide engineering and delivery methods, such as nanocarriers and hydrogel-based systems has enhanced the stability, selectivity, and ability of peptides to target fungal biofilms in experimental models. At the same time, there are important challenges that remain, including their tendency to break down due to proteolytic enzymes, possible cytotoxic effects, difficulties in large scale manufacturing, and regulatory hurdles linked to peptide-based therapies. Overall, AFPs represent a promising and fast developing area of research, but their use in clinical practice is limited. More studies are needed to confirm their safety, effectiveness and practical feasibility for managing biofilm-associated fungal infections.
    Keywords:  Antifungal peptides; antifungal resistance; biofilm disruption; biofilms; therapeutic strategies
    DOI:  https://doi.org/10.1016/j.micpath.2026.108601
  24. J Biomed Mater Res B Appl Biomater. 2026 Jun;114(6): e70105
      Smart bioresponsive hydrogels have emerged as a transformative solution for the management of chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure sores, which are often complicated by persistent inflammation, infection, and biochemical dysregulation. Unlike traditional dressings, these advanced materials are engineered to respond to intrinsic wound stimuli such as pH, reactive oxygen species (ROS), glucose, and enzymatic activity, enabling spatially and temporally controlled drug release. This review comprehensively examines the design principles, biochemical triggers, and functionalization strategies behind stimuli responsive hydrogels. We explore diverse hydrogel classes, including single and multi-stimuli systems, and in-depth functional augmentations, such as antibacterial agents, angiogenic growth factors, and self-healing adhesion mechanisms. A major emphasis is placed on emerging integration with digital health platforms such as wearable biosensors, implantable systems, and AI driven wound analytics, which enable real time monitoring and closed loop drug delivery. Comparative analyses between academic prototypes and existing commercial products are discussed alongside translational barriers related to clinical trials, regulatory challenges, and manufacturing scalability. The review concludes by outlining a prospective roadmap for AI personalized, multifunctional all-in-one hydrogel systems that integrate biomaterials with biosensing and telemedicine capabilities. This manuscript provides a detailed and timely resource for researchers, clinicians, and bioengineers seeking to bridge the gap between hydrogel innovation and clinical impact.
    Keywords:  Internet of Medical Things (IoMT); bioresponsive drug delivery; chronic wound healing; smart hydrogels; wearable biosensors
    DOI:  https://doi.org/10.1002/jbm.b.70105
  25. Can J Microbiol. 2026 Jun 03.
      Pseudomonas aeruginosa<i></i> is a major opportunistic pathogen responsible for severe human infections and is increasingly associated with multidrug resistance and limited treatment options. In this study, we isolated and characterized bacteriophages targeting drug-resistant P. aeruginosa<i></i> strains and evaluated their capacity to disrupt biofilms and modulate biofilm-associated gene expression. Phages recovered from sewage showed broad lytic activity against P. aeruginosa<i></i> and were classified morphologically into the families Podoviridae<i></i> and Myoviridae<i></i>. Two phages, A2 and A4, exhibited the highest lytic activity against the resistant strains examined. Both phages significantly degraded preformed biofilms, with phage A4 showing comparatively stronger antibiofilm activity. In addition, phage exposure altered the expression of several biofilm-associated genes, including pelA<i></i>, htpB<i></i>, bifA</i></i>, psl<i></i>, fimW<i></i>, and wspA<i></i>. A notable finding was the reversal of bifA<i></i> expression from downregulation at 12 h to upregulation at 24 h following treatment with phage A4. Collectively, these results demonstrate that phages A2 and A4 possess strong lytic and antibiofilm activities and are capable of modulating biofilm-associated transcriptional responses in drug-resistant P. aeruginosa<i></i>. The findings support the potential application of bacteriophages as alternative therapeutic agents against drug-resistant biofilm-associated infections.
    DOI:  https://doi.org/10.1139/cjm-2026-0082
  26. Food Chem X. 2026 May;36 103997
      Spontaneous fermentation of Sichuan paocai is shaped by complex microbial and environmental factors, yet phage communities remain understudied. This study presents integrated viromic and metagenomic analysis of radish paocai combined with metabolite profiling to elucidate phage diversity, dynamics, ecological roles, and sources. Time-series metagenomics revealed Lactiplantibacillus increasing from 11% to 71%, while viromics showed phages comprising 78% of viral contigs, with Uroviricota reaching 88% by day 5. Host prediction indicated that 89% of phages targeted Lactiplantibacillus, mainly L. plantarum. Correlation analysis suggested that core phages were associated with fermentation-related metabolites, including volatile compounds (e.g., decanal), implicating that phages might influence metabolism by modulating host activity. Functional annotation showed phage encoded amino acid and carbohydrate metabolism genes, suggesting auxiliary metabolic roles. Source analysis suggested that most phages in radish paocai may be derived from bacterial prophages. This work advances understanding of phage diversity and ecological function in fermented vegetable ecosystems.
    Keywords:  Fermentation; Lactiplantibacillus; Metagenomic; Phage; Viromic
    DOI:  https://doi.org/10.1016/j.fochx.2026.103997
  27. J Clin Periodontol. 2026 Jun 04.
       AIM: Endotoxemia has been proposed as a link between periodontitis and systemic complications through the translocation of lipopolysaccharide (LPS) from inflamed periodontal sites into the bloodstream. This study aimed to investigate subgingival and serum LPS activities and their correlations with periodontal clinical and microbiological parameters.
    MATERIALS AND METHODS: Two-hundred and seventy participants with gingivitis and periodontitis from the SECRETO Oral cohort were included in the study. Serum and subgingival plaque samples were analysed for LPS activity using the recombinant Factor C assay, and subgingival microbiota were profiled by 16S rRNA sequencing. Dysbiosis indices and taxonomic associations were assessed through multivariate regressions and MaAsLin2 models adjusted for clinical and demographic covariates. Functional pathways were inferred using PICRUSt2.
    RESULTS: Serum LPS activities were significantly elevated in periodontitis patients compared to gingivitis patients and correlated with the subgingival microbial dysbiosis index (SMDI). Subgingival LPS was also significantly higher in periodontitis patients and showed strong associations with subgingival bacterial load and SMDI. Subgingival LPS explained 10% of serum LPS variations. Differential abundance analysis identified Fretibacterium as positively associated with both subgingival and serum LPS activities. Functional prediction revealed enrichment of bacterial motility and invasion pathways, with depletion of host defence functions, supporting a mechanistic link between subgingival dysbiosis, LPS translocation and systemic endotoxemia.
    CONCLUSION: These findings provide novel evidence that elevated serum LPS activities are closely linked with periodontitis diagnosis, associated with subgingival dysbiosis, and highlight the periodontal niche as a source of systemic endotoxemia. In addition, it identified Fretibacterium as the main contributor to both subgingival and serum LPS activities.
    Keywords:  dysbiosis; endotoxemia; lipopolysaccharide; periodontitis; subgingival plaque
    DOI:  https://doi.org/10.1111/jcpe.70148
  28. BMC Health Serv Res. 2026 Jun 03.
       BACKGROUND: As population aging accelerates and the burden of chronic diseases increases, the incidence of chronic wounds such as diabetic foot ulcers and pressure injuries continues to rise. This trend not only worsens patient outcomes and quality of life but also strains the healthcare system. Traditional wound care assessments rely on isolated indicators, lack systematic monitoring, and fail to provide comprehensive evaluation throughout the care process, thereby limiting improvements in nursing quality. Based on Donabedian's structure-process-outcome framework, a thorough evaluation system can integrate key elements and multidimensional factors in wound care, supporting evidence-based, standardized nursing management.This study aims to develop a wound care quality evaluation indicator system designed to be clinically applicable and tailored to China's healthcare context, with the goal of promoting standardized practices and improved service quality.
    METHODS: This study used the "structure-process-outcome" model to develop a wound care quality evaluation system. In January 2025, initial indicators were identified via literature review and theoretical analysis. In February, semi-structured interviews refined and expanded the indicator pool. A preliminary draft was finalized after an internal team discussion. From March to April 2025, two rounds of expert consultation were conducted, with 27 experts participating in each via email. Data were analyzed using mean ± Standard Deviation (SD), coefficient of variation, and Kendall's W. Indicator weights were determined using the Analytic Hierarchy Process, yielding a final system with 3 first-level, 9 s-level, and 25 third-level indicators.
    RESULTS: The effective response rates for both rounds of the questionnaire survey reached 100%. The authority coefficients for the experts were 0.874 and 0.889, respectively, indicating high expert reliability. Kendall's coefficient of concordance ranged from 0.169 to 0.181 in the first round and from 0.170 to 0.192 in the second round, reflecting a gradual improvement in consensus among experts. Ultimately, a wound care quality evaluation indicator system was established, comprising 3 first-level indicators, 9 s-level indicators, and 25 third-level indicators.
    CONCLUSIONS: This indicator system is scientifically rigorous and reliable. It demonstrates theoretical potential for clinical applicability, as it is aligned with wound care practices and nursing management to objectively assess wound management quality. However, its practical operability and real-world applicability require further validation through clinical pilot studies.
    CLINICAL TRIAL NUMBER: Not applicable.
    Keywords:  Acute wounds; Chronic wounds; Diabetic foot; Lower extremity venous ulcers; Mixed methods; Nursing evaluation; Nursing quality indicators; Pressure injuries
    DOI:  https://doi.org/10.1186/s12913-026-14823-5
  29. Lancet Respir Med. 2026 Jun 03. pii: S2213-2600(26)00149-9. [Epub ahead of print]
    ECFSPR Steering Group Committee
       BACKGROUND: Since 2018, important advancements in the medical care of people with cystic fibrosis, particularly the introduction and widespread use of highly effective cystic fibrosis transmembrane conductance regulator modulators, have contributed to the adult cystic fibrosis population growing substantially and has led to an increased need for tailored health-care approaches. Our study aimed to analyse the extent to which the clinical characteristics and treatment outcomes of adults with cystic fibrosis have evolved from 2014 to 2024.
    METHODS: The European Cystic Fibrosis Society Patient Registry (ECFSPR), collects annual data for more than 55 000 people with cystic fibrosis. Longitudinal data from 20 countries in Europe with high patient coverage (>85%) from 2014 to 2024 were analysed, representing 80% of the whole ECFSPR cohort. Differences in annual cross-sectional estimates were assessed using regression models.
    FINDINGS: Between 2014 and 2024, the number of adults with cystic fibrosis increased by 45·0%, from 50·9% to 60·5% of the total cystic fibrosis population. The number of adults older than 30 years nearly doubled. Among adults with cystic fibrosis who had not received a transplant, mean percent predicted FEV1 improved from 66·1% to 78·8% (p<0·0001), with most of the gain occurring after 2020. Chronic Pseudomonas aeruginosa infection declined significantly (p<0·0001), whereas mean BMI increased significantly (p<0·0001), halving the proportion of individuals who are underweight. Age-related complications, such as malignancy, increased, whereas cystic fibrosis-specific complications and insulin-treated diabetes declined. The largest improvements were observed in individuals with at least one variant responsive to elexacaftor-tezacaftor-ivacaftor (ETI). The uptake of ETI increased from 2% in 2019 to 71% in 2024, associated with improvements in health indicators.
    INTERPRETATION: From 2014 to 2024, the adult cystic fibrosis population in Europe expanded substantially due to marked improvements in treatment, particularly following the availability of ETI triple therapy from 2018-19 onwards. The growing number of people with CF surviving to adulthood is consistent with substantial effects from improved care and cystic fibrosis transmembrane conductance regulator modulators, such as ETI, and highlight evolving care needs of people with cystic fibrosis.
    FUNDING: None.
    DOI:  https://doi.org/10.1016/S2213-2600(26)00149-9
  30. J Periodontol. 2026 May 30.
       BACKGROUND: This study investigated the effects of non-surgical periodontal therapy (NSPT) on saliva and serum levels of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17, and serum levels of C-reactive protein (CRP) in patients with inflammatory bowel disease (IBD) and/or periodontitis.
    METHODS: The study included 72 participants, 18 in each of the four groups: systemically and periodontally healthy (HH), systemically healthy with periodontitis (HP), IBD and periodontally healthy (IBH) and IBD with periodontitis (IBP). Clinical periodontal parameters and biomarker levels were evaluated at baseline in all groups and 3 months after NSPT in the periodontitis groups. Biomarker levels were analyzed using ELISA.
    RESULTS: At baseline, salivary IL-6 and IL-17 levels were significantly elevated in the IBH and IBP groups compared with those in the HH group (all p < 0.05). NSPT led to significant improvements in periodontal clinical parameters. Following NSPT, significant reductions in salivary IL-6, IL-17, TIM-3, and the serum CRP levels were observed in the IBP group (all p < 0.05). No significant changes in serum IL-6, IL-17, TNF-α, or TIM-3 levels were detected (all p > 0.05). Salivary IL-6 levels showed strong diagnostic potential for distinguishing IBP from HH (AUC = 0.932) and HP from IBP (AUC = 0.889).
    CONCLUSIONS: NSPT may contribute to the modulation of local and systemic inflammation in patients with IBD and periodontitis. Salivary TIM-3 emerged as a potential novel biomarker for periodontal disease detection in this population.
    TRIAL REGISTRATION: This study has been registered in the ClinicalTrials.gov protocol registration system (Identifier: NCT06245278).
    PLAIN LANGUAGE SUMMARY: Periodontitis and inflammatory bowel disease (IBD) are common diseases that are related to each other and have a high risk of occurring together. Dysbiosis and chronic immune activation are common features of both diseases. Cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α), as well as inflammatory markers such as C-reactive protein (CRP), are involved in the inflammatory cascades of both diseases. Although the role of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in the pathogenesis of periodontal disease and IBD is not clearly understood, it is thought to play a role in immunity and disease severity. This study included systemically healthy and periodontally healthy individuals (HH), systemically healthy individuals with periodontitis (HP), periodontally healthy individuals with IBD (IBH), and individuals with IBD and periodontitis (IBP). Serum and saliva samples were collected from all participants at baseline and additionally from individuals with periodontitis after non-surgical periodontal therapy (NSPT). Our findings showed significant improvements in clinical parameters following NSPT, particularly in IBD patients, along with concurrent decreases in saliva TIM-3, IL-6, IL-17, and serum CRP levels. In conclusion, periodontal inflammation may increase systemic immune activation in IBD, and periodontal treatment may offer potential benefits in reducing this burden.
    Keywords:  TIM‐3; TNF‐α; inflammatory bowel disease; interleukin‐17; interleukin‐6; non‐surgical periodontal therapy; periodontitis
    DOI:  https://doi.org/10.1002/jper.70153
  31. Microb Genom. 2026 Jun;12(6):
      Rapid, low-cost genome sequencing has transformed microbiology, advancing efforts to link genetic and phenotypic variation across diverse bacterial systems. Laboratory functional screens now uncover causal mechanisms underlying key traits in simplified systems, such as drug resistance, pathogenicity and metabolic adaptation, while population-scale comparative genomics reveal the immense natural diversity associated with these traits in real-world settings. Despite their complementary strengths, these approaches remain challenging to integrate, especially for researchers without advanced bioinformatics skills. This skills gap can constrain the capacity to reveal the mechanisms underlying microbial traits and evolutionary adaptations. We developed GeneScanner to aid user-friendly analyses of gene- and protein-level variation across large bacterial genome collections. GeneScanner detects genetic variants and amino acid substitutions in homologous sequences to improve functional interpretation of microbial variation. Using synthetic data and three case studies across different species and phenotypes, we show that GeneScanner reliably identifies nucleotide and protein-level variants associated with specific traits. The presented examples highlight the broad applicability of GeneScanner in microbial genomics, enabling research across diverse fields, such as antimicrobial resistance, host-pathogen interactions, microbial evolution, epidemiology and public health.
    Keywords:  antimicrobial resistance; biofilm; bioinformatics; comparative genomics; genetic variation; host association; mutation analysis; variant calling
    DOI:  https://doi.org/10.1099/mgen.0.001714
  32. Gut Microbes. 2026 Dec 31. 18(1): 2681763
      This review explores the pivotal role of the pediatric gut microbiome in shaping early-life development and influencing susceptibility to disease, emphasizing its impact on immune, metabolic, and neurodevelopmental processes. The neonatal period represents a critical window for host-microbiome interactions, beginning at birth when intestinal barrier function is still developing and immune responses remain immature. During this formative stage, rapid microbial colonization and ecological succession are influenced by delivery mode, infant feeding practices, antibiotic exposure, and environmental factors. Beyond bacterial populations, the early-life gut virome composed of bacteriophages and eukaryotic viruses evolves dynamically and contributes to microbial community structure, gene exchange, and immune system maturation. Microbially derived signals and metabolites support the development of mucosal integrity, immune programming, and host microbe equilibrium, with long-term implications for systemic immune function. Breastfeeding fosters the establishment of microbial communities and metabolic profiles associated with immune tolerance, whereas formula feeding and early-life antibiotic use may disrupt normal microbiome development. Alterations in early microbial trajectories have been associated with heightened risk of pediatric conditions, including allergic diseases, obesity, inflammatory bowel disease, and neurodevelopmental disorders. The review further evaluates emerging microbiome-directed strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, considering both their therapeutic promise and current challenges. Collectively, current evidence underscores the early-life gut microbiome as a central determinant of host development and a compelling target for disease prevention strategies.
    Keywords:  Gut microbiome; imbalanced gut; neurodevelopmental disorders; therapeutic; virome
    DOI:  https://doi.org/10.1080/19490976.2026.2681763
  33. Biomater Adv. 2026 Jun 01. pii: S2772-9508(26)00286-4. [Epub ahead of print]188 214988
      Medical implants are crucial for restoring function and regenerating injured organs and tissues. However, beyond design, material properties and placement, the risk of a foreign body reaction (FBR) upon interaction between the host immune system and the biomaterial, as well as the risk of infection at the implant site significantly influence treatment success. FBR has been confirmed to severely affect the integration of medical implants into the host tissue, often leading to therapy failure. This has led to the engineering of several novel biomaterials to improve the biocompatibility and integration of implants. Despite these advancements, the adhesion and colonization of the pathogens onto implant surfaces poses a detrimental risk, resulting in implant-associated infections which is linked to increased morbidity and mortality. Furthermore, biofilm formation on implants can trigger innate immune responses, thereby increasing the complexity of the environment around the implantable materials. This review aims to: first, explore the latest advances in the development of biomaterials targeted at maximizing implant-tissue integration, while minimizing FBR. Second, delve into the interaction between pathogens and biomaterials, highlighting the challenges of implant infection, and discuss current therapeutic strategies.
    Keywords:  Biofilm; Biomaterials; Immune system; Infection; Inflammation; Medical devices
    DOI:  https://doi.org/10.1016/j.bioadv.2026.214988
  34. Appl Environ Microbiol. 2026 Jun 04. e0246225
      Bacteriophage adhesion to intestinal mucus has been proposed as an important mechanism for preventing bacterial infection. However, whether differences in adhesion capacity among closely related phages translate into distinct protective outcomes remains unclear. In this study, we compared two T4-like bacteriophages, S143_2 and W143, to investigate how variation in mucosal adhesion influences antibacterial efficacy and host responses. Both phages exhibited comparable lytic activity against enteropathogenic Escherichia coli (EPEC143) but differed in adhesion capacity to intestinal epithelium. In vitro assays demonstrated that phages adhered to mucus-secreting IPEC-1 cells via a reversible mucus association, with S143_2 displaying significantly stronger adhesion than W143. This difference was further confirmed in vivo, where S143_2 showed higher mucosal retention and a significantly greater mucosa-to-digesta ratio of phage titers in the small intestine. Functionally, enhanced adhesion was associated with improved protective efficacy. In a prophylactic mouse model, pretreatment with S143_2 resulted in reduced body weight loss and lower intestinal pathogen load compared to W143. Furthermore, S143_2 induced a more robust systemic immune response evidenced by elevated serum cytokines and the enrichment of immune-related signaling pathways in the intestinal transcriptome. Together, these findings demonstrate that mucosal adhesion capacity is a critical determinant of phage performance in vivo. Our results highlight that, beyond host range and bactericidal capacity, adhesion properties should be considered a key criterion in the rational selection of bacteriophages for preventing and treating mucosa-associated infections.IMPORTANCEPhages are among the most promising antibiotic alternatives, yet their evaluation has largely focused on bacterial host range and lytic activity. Our findings highlight mucosal adhesion as a previously overlooked but decisive factor in phage efficacy when targeting mucosa-associated infections. Phages with stronger epithelial adhesion exhibit superior protection and immune modulation in the gut, underscoring that adhesion capacity should be integrated as a key criterion in the rational selection and engineering of therapeutic phages.
    Keywords:  immune response; phage adherence; phage therapy; protective efficacy
    DOI:  https://doi.org/10.1128/aem.02462-25
  35. J Drugs Dermatol. 2026 Jun 01. 25(6): 523-529
       BACKGROUND: Acne is the most prevalent skin disease globally, with a significant burden and limited therapeutic innovation. Although it has a multifactorial etiology, Cutibacterium acnes (C acnes) overgrowth is a key factor in driving inflammation in acne. Bacteriophages are a novel mechanism that can specifically target C acnes and are found in greater abundance on healthy skin compared to acne-prone skin.
    OBJECTIVES: To study the safety and efficacy of phages and salicylic acid (SA) in acne, and to analyze their mode of action and effect on microbiome diversity.
    METHODS: A randomized double-blind placebo-controlled study was conducted on 90 participants for 8 weeks. Males and females 12 to 35 years old with mild to moderate acne were enrolled in placebo, phage, and phage + SA arms. Clinic visits at baseline, week 4, and week 8 collected safety data, VISIA imaging, lesion counts, IGA scores, and microbiome samples.
    RESULTS: Phage treatment demonstrated an excellent safety profile. Participants in both phage and phage + SA arms showed significant improvement (P&lt;0.05) over baseline at 8 weeks. Phage application resulted in a statistically significant (P&lt;0.05) decrease of C acnes on the skin compared to placebo. Notably, phage use over 8 weeks significantly increased microbiome diversity, a marker of long-term skin health.
    CONCLUSION: This study shows the potential of bacteriophages to be a highly promising modality with a unique mode of action for the treatment of acne. Beyond short-term lesion improvement, phage-induced enhancement of microbiome diversity suggests potential for durable, long-term skin health benefits. &nbsp.
    DOI:  https://doi.org/10.36849/JDD.9346
  36. Indian J Pediatr. 2026 Jun 06.
      Artificial intelligence (AI) technologies such as machine learning (ML), deep learning (DL), predictive analytics and other tools are rapidly changing pediatric health care, using large amounts of health data. AI tools aid in triage, real-time monitoring and risk stratification in acute care settings, towards improving overall outcomes and fewer complications. During newborn resuscitation, AI analyses real-time data, can guide decisions and enhance training. Computer vision systems with AI tools can generate reliable neonatal bilirubin estimates without the need for blood sampling. AI technology is also being used in the management of necrotising enterocolitis, respiratory distress syndrome, and screening and early diagnosis of retinopathy of prematurity. ML models assist in detecting brain injuries on MRI for conditions such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage; MRI biomarkers can be analyzed using AI to predict neurodevelopmental outcomes. AI-based clinical decision support systems have been deployed to enhance workflows and outcomes by early detection of disease, reducing medication errors and help clinicians improve decision-making. However, there remain ethical and practical challenges in the use of AI including data privacy, the need for high-quality pediatric datasets, rigorous clinical validation and transparency, to ensure that AI strengthens clinical judgement and is trustworthy.
    Keywords:  Artificial intelligence; Clinical decision support; Deep learning; Machine learning
    DOI:  https://doi.org/10.1007/s12098-026-06254-1
  37. J Food Prot. 2026 Jun 04. pii: S0362-028X(26)00130-4. [Epub ahead of print] 100825
      Biofilms formed on food-contact surfaces and processing equipment serve as persistent bacterial reservoirs that lead to recurrent food contamination and foodborne illnesses. Conventional sanitizers and antimicrobial treatments often fail to remove these structured microbial communities, which are protected by matrixes formed from extracellular polymeric substances (EPS), the presence of metabolically dormant persister cells, and various adaptive resistance mechanisms. Natural compounds (NCs) are increasingly viewed as alternative antibiofilm agents, but evidence supporting their effectiveness remains fragmented, and studies integrating molecular mechanisms and practical applications in food-processing systems are scarce. This review evaluates diverse NCs, including plant-derived phenolics, alkaloids, and terpenoids, as well as various marine and microbial metabolites, for their potential as robust alternatives for biofilm control. Unlike traditional biocides, NCs display multifaceted antibiofilm activities that target key biofilm developmental stages by inhibiting initial bacterial attachment and swarming motility, disrupting quorum sensing and c-di-GMP signaling, and destabilizing the EPS scaffold. NCs also effectively eradicate recalcitrant persister bacteria by disrupting membranes, inducing oxidative stress, and suppressing virulence factors. We specifically focus on advanced application strategies, such as nanotechnology-based delivery systems, surface functionalization coatings, and synergistic combinations with conventional sanitizers, which are tailored for biofilm eradication on food-processing environments and food-contact materials. Collectively, these NC-based interventions support a conceptual shift from bactericidal approaches toward ecological behavior-modulating biofilm management to enable more sustainable and effective control of foodborne pathogens across the food supply chain.
    Keywords:  Biofilm; Extracellular polymeric substance (EPS); Foodborne pathogen; Nanotechnology; Natural compound; Quorum sensing (QS)
    DOI:  https://doi.org/10.1016/j.jfp.2026.100825
  38. Ocul Immunol Inflamm. 2026 Jun 01. 1-14
       PURPOSE: This study aims to systematically analyze and map the research landscape of gut microbiota in autoimmune eye diseases through comprehensive bibliometric analysis.
    METHODS: We retrieved 261 relevant publications from the Web of Science Core Collection (2010-2024) and analyzed them using CiteSpace, VOSviewer, and biblioshiny.
    RESULTS: The results reveal three distinct developmental phases: initial exploration (2010-2015), emerging growth (2016-2020), and rapid expansion (2021-2024). International collaboration analysis identified the United States and China as leading contributors, with strong European research clusters. Core research themes centered on gut microbiota-host immune system interactions, inflammatory pathways, and disease-specific microbial signatures. Temporal analysis demonstrated evolution from fundamental studies to mechanistic investigations and therapeutic applications. Citation analysis identified landmark studies that established gut-eye axis mechanisms and pathogenic processes. Analysis of research hotspots revealed increasing focus on personalized medicine approaches, multi-omics integration, and microbiome-based therapeutics.
    CONCLUSION: This study provides a comprehensive overview of the field, identifies research frontiers, and proposes future research directions, namely, methodological advancement, mechanistic understanding, and clinical translation.
    Keywords:  Autoimmune eye diseases; bibliometric analysis; gut microbiota; gut-eye axis; research trends
    DOI:  https://doi.org/10.1080/09273948.2025.2606819
  39. Microb Biotechnol. 2026 Jun;19(6): e70394
      Acute oak decline (AOD) is a complex disease of oak trees (Quercus spp.) which results in bleeding stem cankers and potential tree mortality. A polymicrobial complex is implicated in causing AOD, of which the most commonly isolated species are Brenneria goodwinii and Gibbsiella quercinecans. Bacteriophages (phages), natural predators of bacteria, can act as biocontrol agents that reduce bacterial infections in trees. In this study, the first phages that lyse B. goodwinii and G. quercinecans, BREN6 and GIB1 phages respectively, were isolated from AOD-impacted trees. Genomic analyses and transmission electron microscopy showed that BREN6 is a novel phage type with siphovirus morphology, whereas GIB1 possesses characteristics typical of N4-like phages. While in vitro assays showed that each phage could effectively reduce their hosts' population growth for at least 24 h, application of the phages to either single or dual species communities of B. goodwinii and G. quercinecans in the stems of oak saplings showed that the phages had a minimal impact on their host populations, and in some trees actually resulted in higher bacterial populations. Our data show that the application of these phages does not alter the in planta population dynamics between B. goodwinii and G. quercinecans, and emphasises the importance of assessing phage effectiveness within natural settings.
    Keywords:  Quercus spp.; bacteriophage; plant pathogens
    DOI:  https://doi.org/10.1111/1751-7915.70394
  40. J Oral Biosci. 2026 Jun;pii: S1349-0079(26)00050-2. [Epub ahead of print]68(3): 100782
       BACKGROUND: Porphyromonas gingivalis is a periodontal pathogen that primarily mediates its interactions with host tissues and other bacteria through fimbrial structures. The diversity and assembly mechanisms of its fimbriae are fundamental to understanding its pathogenicity, and its roles in periodontal and systemic diseases. This bacterium mainly expresses two types of fimbriae, FimA and Mfa1. Recent structural and genetic studies have demonstrated that these fimbriae conform to the conserved assembly principles of Type V fimbriae shared by Bacteroidia-class bacteria.
    HIGHLIGHTS: This review focuses on Mfa1 fimbriae, and it summarizes the current knowledge on their assembly mechanisms, genetic diversity, components, and strain-dependent structural variations. In particular, the balance between conserved structural features and strain-specific variations is discussed, focusing on the molecular basis of fimbrial formation and incorporation of accessory proteins. The discussion centers on the major fimbrillin Mfa1 anchor protein, Mfa2, accessory proteins, Mfa3 and Mfa4, and the variable Type IX secretion system-dependent accessory protein, Mfa5.
    CONCLUSION: By integrating recent findings, this review emphasizes how a conserved Type V assembly framework, combined with variations in accessory components, enables Mfa1 fimbriae to maintain structural stability, while accommodating strain-dependent diversity. This synthesis provides an updated perspective on the balance between stability and strain-dependent structural adaptability in Mfa1 fimbrial systems, and their potential implications for fimbrial assembly, bacterial adhesion, and host-microbe interactions.
    Keywords:  Mfa1 fimbriae; Periodontal diseases; Porphyromonas gingivalis; Type V fimbriae
    DOI:  https://doi.org/10.1016/j.job.2026.100782
  41. Respir Med. 2026 Jun 03. pii: S0954-6111(26)00293-3. [Epub ahead of print] 108925
       INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by mutations in the CFTR gene. In Turkiye, high genetic diversity and consanguinity contribute to a heterogeneous CFTR variant spectrum; however, genotype-phenotype data remain limited.
    METHODS: This retrospective study analyzed 92 Turkish CF patients (36 homozygous, 56 compound heterozygous) to characterize CFTR variant diversity and clinical outcomes. Next-generation sequencing (NGS) was performed and confirmed by Sanger sequencing. Clinical data were analyzed using chi-square and nonparametric tests (p < 0.05).
    RESULTS: A total of 46 distinct CFTR variants were identified. The most frequent were F508del (24%), followed by Y515X (7.33%), G542X (6%), N1303K (5.33%) and D110H (4%). Meconium ileus (p = 0.017) and CF-related diabetes mellitus (p = 0.013) were significantly more frequent among homozygous patients. Pseudomonas aeruginosa and Staphylococcus aureus were the most prevalent pathogens. CFTR modulator therapy eligibility was significantly higher among compound heterozygous patients (p = 0.007). Non-missense variants were associated with higher sweat chloride levels and more frequent severe pancreatic insufficiency and abnormal fecal fat quantification compared with missense variants (p = 0.037; p = 0.001; p = 0.033).
    CONCLUSION: This study highlights the heterogeneous CFTR variants in Turkiye and suggests genotype-phenotype correlations. Homozygous patients tended to show more severe gastrointestinal and endocrine involvement, while compound heterozygotes may exhibit comparatively milder disease features and higher treatment eligibility.
    Keywords:  CF-related diabetes mellitus; CFTR; Cystic Fibrosis; Genotype-Phenotype Correlation; Meconium ileus; Modulator therapy
    DOI:  https://doi.org/10.1016/j.rmed.2026.108925
  42. Infect Immun. 2026 Jun 04. e0069325
      Muco-obstructive airway diseases result in an increase in mucus accumulation and a decrease in mucus clearance. MUC5B is the most abundant secreted mucin in the human airways, and MUC5B mucin strands dimerize to create the mucus mesh network in the healthy respiratory tract. In muco-obstructive airway diseases like cystic fibrosis (CF), immune cells and bacteria release enzymes that degrade MUC5B into smaller fragments that become entangled and compacted, contributing to pathogenesis. We utilized synthetic cystic fibrosis sputum media (SCFM) to examine how mucin polymers can impact Staphylococcus aureus, a common CF pathogen that persists despite highly effective modulator therapies to correct CF disease. We found that low-molecular-weight (LMW) mucin negatively impacts S. aureus survival and biofilm biomass compared to high-molecular-weight (HMW) mucin. Adding extracellular DNA to SCFM with LMW mucin was not sufficient to restore growth. LMW mucin had a broad negative impact on S. aureus laboratory strains and CF clinical isolates. We next tested other CF pathogens, including Pseudomonas aeruginosa and nontypeable Haemophilus influenzae, and saw no significant differences in growth in HMW or LMW mucin. LMW mucin did not significantly impact Staphylococcus epidermidis growth, indicating that there may be specific interactions with S. aureus. Overall, this work highlights how interactions with pathogenic mucins may limit S. aureus growth in the diseased airways while supporting low-level persistence, and its ability to thrive in the presence of longer mucin strands may help explain why S. aureus is well adapted to survive in the healthy respiratory tract.
    Keywords:  Staphylococcus aureus; aggregation; biofilms; mucin; muco-obstructive airway disease
    DOI:  https://doi.org/10.1128/iai.00693-25
  43. Diabetes Metab Syndr Obes. 2026 ;19 593437
       Purpose: The care of diabetic foot ulcers (DFU) continues to be a notable clinical challenge. The efficacy and safety of stem cell therapies versus conventional treatments for DFU are debated. Cross-sectional analyses of meta-analyses enable structured comparisons of overlapping reviews, facilitate the identification of inconsistencies, and support evidence-based decision-making when conclusions differ. This study aimed to conduct a cross-sectional analysis of existing meta-analyses comparing stem cell and conventional treatments for DFU outcomes to identify the highest-quality available evidence and clarify areas of consistency and discrepancy.
    Methods: We systematically searched for meta-analyses that investigated stem cell therapies versus conventional treatments for DFU. The complete electronic search strategies for all databases are provided in accordance with PRISMA 2020 recommendations. Methodological quality was assessed using the Oxford Levels of Evidence and original AMSTAR instrument. Data abstraction and quality evaluation were performed independently, and the Jadad decision algorithm was applied to determine the meta-analysis providing the most methodologically robust evidence.
    Results: Nine meta-analyses were included in this study. Five were categorized as Level II evidence, while the remaining four were classified as Level III evidence. The AMSTAR scores ranged from 7 to 10 (median 9). The Jadad algorithm identified the most robust meta-analysis consistently showing improved ulcer healing rates (P < 0.0001), greater pain-free walking distance (P < 0.00001), lower amputation rates (P < 0.0001) compared with conventional treatments. Furthermore, the incidence of adverse events in the stem cell groups was lower compared to conventional treatments (P < 0.001).
    Conclusion: The study indicated that stem cell therapy appeared to be a promising therapeutic option for improving clinical outcomes. However, conclusions should be interpreted with caution due to overlapping primary studies, heterogeneity, and the secondary nature of this cross-sectional evaluation. Moreover, no clear evidence of increased serious adverse events was identified in the highest-quality meta-analysis.
    Keywords:  Jadad decision algorithm; conventional treatment; diabetic foot ulcer; meta-analysis; stem cell therapy
    DOI:  https://doi.org/10.2147/DMSO.S593437
  44. Brief Bioinform. 2026 May 04. pii: bbag269. [Epub ahead of print]27(3):
      The shift of artificial intelligence for antimicrobial resistance (AI-AMR) from proof-of-concept studies to clinically embedded decision support critically hinges on establishing rigorous reproducibility, interpretability, and evaluation standards aligned with antimicrobial stewardship and patient safety. This review traces the field's evolution from rule-based gene matching through classical machine learning to deep learning models, foundation models, and generative models and proposes a pragmatic standards framework covering dataset curation, multi-site external validation, transparent model cards, and systematic error-cost analyses. Historically, progress was catalysed by curated resistome ontologies; modern practice demands FAIR-aligned curation, explicit bias and data-leakage audits, and prospective temporal and external geographic validation guided by emerging healthcare AI guidelines. To translate accuracy into safer prescribing, the review advocates cost-sensitive evaluation that quantifies false-positive and false-negative harms, integrates stewardship metrics (time-to-effective therapy, spectrum narrowing, days of therapy), and facilitates continuous post-deployment monitoring. Looking forward, federated learning, multimodal and foundation architectures, generative models for antimicrobial and peptide design, and explainable interfaces usable at the point-of-care are poised to reshape trustworthy and clinically deployable AI-AMR. The review concludes with a checklist for implementers: FAIR and diversity-by-design data curation, prospectively specified multi-site validation, standardised governance-linked model cards, and explicit stewardship-oriented error-cost trade-offs.
    Keywords:  antimicrobial resistance; artificial intelligence; explainable AI; model interpretability; reproducibility crisis
    DOI:  https://doi.org/10.1093/bib/bbag269
  45. J Cyst Fibros. 2026 May;pii: S1569-1993(26)00089-5. [Epub ahead of print]25(3): 443-449
      Gastrointestinal symptoms are common in CF, present in at least 65%, and possibly as high as 98% of people with CF (PwCF) and up to 20% reporting these symptoms to be moderate to severe. Chronic GI symptoms including flatulence, bloating, nausea, fullness and abdominal distension experienced by PwCF are likely more complex than a single structural etiology, and may be attributable to or amplified by a complex interaction of biopsychosocial factors. Here we explore the "toxic tetrad" of known abnormalities throughout the CF gut: maldigestion, dysbiosis, inflammation and dysmotility, all of which are inter-related and ultimately contribute to the final end result of chronic GI symptoms for PwCF. Furthermore, we consider diagnostic and therapeutic modalities for dysmotility and dysbiosis in the general population and consider potential applicability and limitations in PwCF.
    Keywords:  Disorder of gut brain interaction; Dysbiosis; Dysmotility; GI; Gastrointestinal symptoms; Inflammation; Maldigestion
    DOI:  https://doi.org/10.1016/j.jcf.2026.03.023
  46. Adv Wound Care (New Rochelle). 2026 May 31. 21621918261450959
       BACKGROUND: Diabetic foot ulcers (DFUs) represent one of the most severe complications of diabetes mellitus and are associated with limb loss, excess mortality, and substantial health care costs. Although DFUs are often approached as a localized wound condition, increasing evidence suggests that they reflect advanced systemic vascular and metabolic disease. However, large real-world longitudinal studies integrating wound outcomes, survival, and economic burden remain scarce.
    OBJECTIVES: The objective of this study is to evaluate long-term clinical outcomes, survival, and health care costs associated with DFUs in a large real-world cohort and to identify factors independently associated with mortality and limb loss.
    METHODS: We conducted a retrospective longitudinal cohort study including 5,698 adult patients with diabetes treated for active DFUs at a tertiary referral hospital. Minor and major amputations, survival outcomes, health care utilization, and estimated direct hospital costs were analyzed. Time-to-event analyses included Kaplan-Meier estimation, competing-risk regression, and multivariable Cox proportional hazards models. Disease trajectories were further explored using multistate modeling.
    RESULTS: During follow-up, 290 major amputations were recorded. Patients undergoing major amputation showed significantly worse survival compared with nonamputated patients or those with minor amputations (log-rank p < 0.001). Mean survival after major amputation was 35.3 months, compared with more than 47 months in patients without major limb loss. Five-year overall survival was 61.8%, decreasing to 32.1% among patients with major amputation. Increasing age, peripheral arterial disease, ischemic heart disease, end-stage renal failure, and prior major amputation were independently associated with mortality. Male sex emerged as the main independent predictor of major amputation in adjusted competing-risk models. DFU-related care was associated with high health care utilization and progressively escalating hospital costs.
    CONCLUSIONS: DFUs should be regarded as a marker of advanced systemic disease rather than an isolated wound condition, given their strong association with long-term mortality, limb loss, and economic burden. Early risk stratification and integrated multidisciplinary care strategies are essential to improve outcomes in this high-risk population.
    Keywords:  amputation; cohort study; diabetic foot ulcer; health care costs; peripheral arterial disease; survival
    DOI:  https://doi.org/10.1177/21621918261450959
  47. Microb Drug Resist. 2026 Jun 05. 10766294261457994
      Globally, Acinetobacter baumannii has emerged as an important nosocomial pathogen and as highly resistant to clinically relevant antibiotics, namely, carbapenems. In this study, we aimed to determine the epidemiological profile and the imipenem (IPM) resistance rate of a clinical collection of A. baumannii isolates. This study was carried out at the Central Laboratory of the Oran Regional University Military Hospital (Hôpital militaire régional universitaire d'Oran) over a period of 7 years (January 2010-December 2016). The frequency of A. baumannii isolates was not constant over the 7 years; however, an increasing trend was observed. Among the 168 isolates, the majority was isolated from male patients (n = 131, 78%). Patients in the intensive care unit had a higher risk of developing A. baumannii infection (76%) compared to other hospital services, and protected distal pulmonary samples were the main site of isolation of A. baumannii isolates (34%). Among the collected isolates, 106 were IPM resistant and exhibited multidrug phenotypes. These results confirm the multidrug-resistant nature of A. baumannii and its nosocomial behavior. The emergence of this bacterial species represents a serious therapeutic and epidemiological problem, hence the need for the establishment of a system for monitoring the microbial environment of the hospital and the strict application of hygiene measures.
    Keywords:  Acinetobacter baumannii; epidemiology; imipenem resistance; multidrug resistance; nosocomial infections
    DOI:  https://doi.org/10.1177/10766294261457994
  48. J Cyst Fibros. 2026 Jun 02. pii: S1569-1993(26)01641-3. [Epub ahead of print]
       BACKGROUND: Cystic fibrosis (CF) care utilization decreased during the COVID-19 pandemic. This study aims to describe the utilization of recommended components of CF care over the past five years to determine the extent to which lower utilization has persisted through 2023.
    METHODS: We summarized care utilization patterns for individuals participating in the CF Foundation Patient Registry from 2019-2023 based on recommended components of the CF care as well as a composite indicator of comprehensive CF care defined as ≥4 visits, ≥4 pulmonary function tests, ≥4 bacterial cultures and at least one multidisciplinary assessment per year. We compared the proportion of individuals who received comprehensive care every year, in some years, or never from 2019-2023, stratifying by adult and pediatric populations.
    RESULTS: 27,719 individuals met the inclusion criteria. CF care utilization was higher among children versus adults for all indicators except use of telehealth. For most indicators, utilization of care was lowest in 2020, increased during 2021-2023, but did not return to 2019 levels. The percentage of adults with ≥4 outpatient visits fell from 55% in 2019 to 22% in 2023, while the percentage of those with ≥4 bacterial cultures fell from 45% in 2019 to 17% in 2023. Using a composite measure of comprehensive care, 44% of adults met criteria in 2019, compared to 17% in 2023. In children, 45% met the composite measure in 2019 compared to 38% in 2023.
    CONCLUSIONS: CF care utilization had not returned to 2019 levels as of 2023. From 2021-2023, the proportion of people receiving specific components of the CF care each year had stabilized. Care utilization rates may be influenced by widespread use of CFTR modulator therapy, as well as factors such as insurance status, health status, presence of CF complications, individual preference, and habituation to less frequent clinic visits during the pandemic.
    Keywords:  Adult care; CF Care utilization; Cystic fibrosis; ETI; Models of care; Pediatric care; Post-COVID-19
    DOI:  https://doi.org/10.1016/j.jcf.2026.05.018
  49. Int J Qual Stud Health Well-being. 2026 Dec 31. 21(1): 2682039
       BACKGROUND: Home healthcare includes many safety challenges in wound care due to the unique and varied care conditions. In this specific context, there is a paucity of knowledge regarding how healthcare professionals ensure safety in wound care management. This study aimed to explore how patient safety risks are experienced and managed in wound care by healthcare professionals in Swedish home healthcare settings.
    DESIGN: The study was based on a qualitative, explorative research design with an inductive approach.
    METHOD: Individual interviews were conducted with 16 healthcare professionals with wound care experience in home healthcare services. The data was analysed based on qualitative content analysis.
    RESULTS: Two overarching themes and six subthemes were identified as influencing patient safety, presenting challenges that healthcare professionals were required to manage on a daily basis: "Working blindfolded" reflected challenges with the many healthcare professionals involved in wound care. Challenges also comprised fragmented communication pathways and varying knowledge levels, which at times required them to work without the full information or knowledge needed. "Working with hands tied" concerned how registered nurses were obliged to work within specific frameworks with limited possibilities to act. Preventative work was curtailed, reaching agreements with other members of the wound care team that proved challenging in a diverse and dynamic environment.
    CONCLUSION: The findings predominantly indicated challenges related to organisational preconditions that could jeopardise patient safety. In certain instances, the professionals were unable to resolve these issues, which resulted in an imminent risk of adverse events and prolonged wound healing.
    Keywords:  Patient safety; healthcare professionals; home healthcare; municipal care; qualitative methods; wound care
    DOI:  https://doi.org/10.1080/17482631.2026.2682039
  50. Nature. 2026 Jun 03.
      
    Keywords:  Computer science; Health care; Machine learning; Medical research
    DOI:  https://doi.org/10.1038/d41586-026-01691-6
  51. J Vis Exp. 2026 May 15.
      Chronic infections such as those in cystic fibrosis (CF) are sustained by small, highly tolerant Pseudomonas aeruginosa aggregates that persist despite immune and therapeutic pressures. Unlike classical biofilms, these aggregates represent a distinct pathogenic unit - microscale, spatially organized communities that maintain structural integrity and physiological homeostasis under host-induced stress. However, the mechanisms that enable aggregates to remain intact under these conditions, and whether these homeostatic processes can be selectively disrupted, remain poorly defined. A key barrier to addressing this gap has been the lack of tools capable of capturing the dynamic, spatially resolved processes that link physiological stress to structural stability and collapse in real time. This study presents an integrated imaging and analytical workflow to quantify aggregate responses to host-relevant stressors. Using the voltage-sensitive dye DiBAC4(5), membrane depolarization was monitored as an early indicator of physiological disruption within aggregates formed in synthetic cystic fibrosis sputum medium (SCFM2). High-resolution time-lapse confocal microscopy enables visualization of aggregates in both stable and stress-induced states, while image segmentation and voxel-based analysis provide quantitative mapping of spatial heterogeneity in membrane integrity and aggregate disassembly at single-cell resolution. This workflow establishes a reproducible and adaptable platform for linking physiological stress to structural outcomes in multicellular bacterial aggregates. By enabling quantitative dissection of the processes that preserve - or compromise - aggregate integrity, this approach provides a critical foundation for identifying and targeting the homeostatic mechanisms that underpin aggregate resilience, advancing new strategies to disrupt this clinically significant mode of bacterial persistence.
    DOI:  https://doi.org/10.3791/70682
  52. Mol Biol Rep. 2026 Jun 02. pii: 869. [Epub ahead of print]53(1):
      Acinetobacter baumannii is a rapidly evolving opportunistic pathogen that has developed strategies to resist multiple antimicrobials and evade the host immune system. Its global emergence as a multidrug-resistant (MDR) pathogen has severely limited treatment options and increased mortality in hospital settings. Virulence factors associated with the cell envelope and outer membrane vesicles play central roles in bacterial survival and pathogenicity. In this context, this review aims to provide a concise overview of the virulence apparatus present on the surface of A. baumannii and evaluate its role in bacterial survival, pathogenicity, and host-pathogen interactions, while also exploring its potential as a therapeutic target. A scoping review of the published literature was conducted to address the structure, function, and host-interaction dynamics of surface-associated virulence factors and secreted outer membrane vesicles (OMVs) along with their translational therapeutic potential. Virulence factors associated with the bacterial cell envelope and OMVs play integral roles in the survival and pathogenicity of A. baumannii. These surface components are involved in biofilm formation, adhesion to both biotic and abiotic surfaces, and modulation of host cell responses. Their surface accessibility and functional conservation make them attractive therapeutic targets and candidate vaccine antigens. The efficacy of subunit vaccines targeting components of the virulence apparatus has also been explored in several studies. Additionally, secreted OMVs perform diverse biological functions and have demonstrated immunogenic potential. However, strategies targeting single virulence determinants have often shown limited efficacy due to functional redundancy and adaptive plasticity, whereas multi-target approaches (utilising combinations of multiple surface-associated virulence factors of A. baumannii) may represent as one of the effective anti-virulence therapy approaches to prevent disease progression caused by MDR strains, ultimately contributing to improved therapeutic outcomes and reducing the burden of hospital-acquired infections.
    Keywords:   Acinetobacter baumannii ; Antimicrobial resistance; Biofilm; Host cell adhesion; Outer membrane vesicles; Virulence factor
    DOI:  https://doi.org/10.1007/s11033-026-12058-5