bims-fagtap 2026-02-01 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2026–02–01
39 papers selected by
Luca Bolliger, lxBio

Broth Optical Density-Based Assessment for Phage Therapy: Turbidity Reduction, Antibacterial Virulence, and Time-Kill.
Bacteriophage Therapy: Overcoming Antimicrobial Resistance Through Advanced Delivery Methods.
Phage Therapy at the Crossroads Between Clinical Promise and Regulatory Challenge.
The Role of Genomics in Advancing and Standardising Bacteriophage Therapy.
Phage Therapy: Application and Related Problems-A Review.
Bacteriophage Therapy Against Klebsiella Pneumoniae.
Military health applications of bacteriophage: opportunities and challenges.
Pseudomonas aeruginosa Phage Cocktails: Rational Design and Efficacy Against Mouse Wound and Systemic Infection.
The Forgotten History of Bacteriophages in Bulgaria: An Overview and Molecular Perspective on Their Role in Addressing Antibiotic Resistance and Therapy.
Phage cocktails containing a dual-receptor Phikzvirus suppress resistance evolution in Pseudomonas aeruginosa.
Feature-Based Growth Curve Classification Enables Efficient Phage Discrimination.
[Advances in frontier technologies and innovative applications for the prevention and control of hospital infections associated with multidrug-resistant bacteria].
Understanding and Advancing Wound Healing in the Era of Multi-Omic Technology.
The Wound Microbiome in Chronic Wounds: A Biomarker and Therapeutic Target.
Salmonellosis as a One Health-One Biofilm Challenge: Biofilm Formation by Salmonella and Alternative Eradication Strategies in the Post-Antibiotic Era.
Peptides in wound healing: A comprehensive review of their roles, challenges, and hydrogel-based delivery systems.
Two virulent bacteriophages targeting carbapenem-resistant Raoultella planticola.
Special Issue: "Bacteriophages and Biofilms 2.0".
Randomized, Negative-Controlled Pilot Study on the Treatment of Intramammary Staphylococcus aureus Infections in Dairy Cows with a Bacteriophage Cocktail.
Bacteriophage endolysins: A promising therapeutic strategy against drug- resistant Staphylococcus aureus.
AIEgen-Based Photothermal Nanoparticles With Dual Antibacterial and Anti-Inflammatory Activities for Enhanced Healing of Infected Diabetic Wounds.
Comprehensive genome analysis uncovers the diversity of jumbo phages in the pig gut microbiome.
Phage therapy against methicillin-resistant Staphylococcus pseudintermedius: a novel strategy for canine pyoderma.
Mechanisms of Pseudomonas aeruginosa Resilience Against Antibiotic Treatment and Outlooks of Emerging Treatment Strategies.
Comparative Evidence on Negative Pressure Therapy and Hyperbaric Oxygen Therapy for Diabetic Foot Ulcers: A Systematic Review of Independent Effectiveness and Clinical Applicability.
Microbial therapeutics for canine periodontal disease: current status and future perspectives.
Phage PM16 Therapy Induce Long-Term Protective Immunity Against Proteus mirabilis via Macrophage Priming.
Cyclic Peptides in Wound Hydrogels: Current Advances and Future Directions.
Nitric Oxide-Releasing Gels in the Context of Antimicrobial Stewardship, Biofilm Management, and Wound-Repair Biology.
Novel Koutsourovirus phages disrupt clinical multidrug-resistant Enterobacter cloacae biofilms: genomic and functional characterization.
The Overlooked Power of Targeted Phage Lysis in Bacterial Biosensing.
Mycobacterial non-homologous end joining is required for antiphage defense.
The Airway Microbiome in Chronic Obstructive Pulmonary Disease (COPD): A Guide for Clinicians.
Therapeutic Potential of a Novel Stenotrophomonas maltophilia Phage XAN_XB1: Isolation, Characterization, Genome Analysis and Evaluation in Mice Model.
Exploring Exercise as Airway Clearance in Cystic Fibrosis: A Qualitative Study From the ExACT-CF Feasibility Trial.
How ready are we to use artificial intelligence in our fight against Antimicrobial resistance? An ESGAID and EAAS perspective.
The role of the gut microbiome in MDRO colonisation and infection.
Organ-on-a-chip in oral medicine: Emerging approaches and applications.
Gut and Joint Microbiome and Dysbiosis: A New Perspective on the Pathogenesis and Treatment of Osteoarthritis.

Viruses. 2026 Jan 10. pii: 97. [Epub ahead of print]18(1):

Broth Optical Density-Based Assessment for Phage Therapy: Turbidity Reduction, Antibacterial Virulence, and Time-Kill.

Stephen T Abedon.

  Phage therapy is the use of bacterial viruses, or bacteriophages, as antibacterial agents. It has been in use for over 100 years and is becoming increasingly common clinically. The first steps of phage therapy include identification of bacteria to be targeted and then obtaining phages with appropriate host ranges. This is followed by various approaches to in vitro phage characterization. Increasingly common for phage phenotypic characterization is the use of kinetic microtiter plate readers. They can both decrease workloads and increase throughput, especially relative to analyses that require plating on agar-based media. These colorimetric/turbidimetric/optical density approaches primarily assess phage-induced culture-wide bacterial lysis, in the shorter term, or instead the phage potential to suppress phage-resistance evolution over longer time frames. Considered here are methods relevant to phage characterization especially for phage-therapy purposes. Discussed are turbidity-reduction assays, determinations of phage antibacterial virulence, and related time-kill curve analysis. All are or can be optical density-based approaches to assessing phage-based bacterial reduction. Emphasis is placed on consideration of the utilities, limitations, and intersections of these similar methods. Emphasized is that the start of "Deviation"-where phage-treated culture turbidity diverges from phage-free controls-may represent a superior endpoint for such optical density-based bacterial-reduction protocols.

Keywords:  96-well plate; bacterial growth reduction; bacteriophage; bacteriophage therapy; kinetic assay; lysis profile; optical density; time kill; time-kill; time-killing

DOI:  https://doi.org/10.3390/v18010097
Molecules. 2026 Jan 17. pii: 324. [Epub ahead of print]31(2):

Bacteriophage Therapy: Overcoming Antimicrobial Resistance Through Advanced Delivery Methods.

Marcin Wacnik, Emilia Hauza, Aneta Skaradzińska, Paulina Śliwka.

  Microbial resistance to antibiotics necessitates the development of alternative treatments to address the challenges posed by severe bacterial infections. Bacteriophages are regaining clinical relevance, but the effectiveness of phage therapy depends directly on the route of administration and the carrier used. This review provides a critical overview of the therapeutic potential of phages, emphasizing different strategies for delivery to the site of infection. We focus on the preclinical and clinical data on phage therapies using various routes of administration, such as oral, intravenous, inhalation, topical, and local administration to joints and bones. In view of different phage formulations, including liquid suspension, phages immobilized in polymers or liposome-based carriers, we highlight the potential challenges and obstacles that may affect phage stability and bioavailability and limit the successful outcome of therapy. This review serves to enhance the understanding of the integration of materials engineering with clinical practice and production standardization, to address these issues. Additionally, a clear knowledge of the bacteriophage and pharmacokinetics of phage preparations is necessary to implement safe and efficacious bacteriophage treatment in the era of antimicrobial resistance.

Keywords:  AMR; bacteriophages; delivery strategies; hydrogels; liposomes; phage therapy; routes of administration

DOI:  https://doi.org/10.3390/molecules31020324
Pharmaceuticals (Basel). 2026 Jan 16. pii: 162. [Epub ahead of print]19(1):

Phage Therapy at the Crossroads Between Clinical Promise and Regulatory Challenge.

Anna Gallina, Matteo Gallina, Andrea Cona, Patrizio Vitulo, Alessandra Mularoni, Alessio Provenzani.

  Bacteriophage (phage) therapy, including monophage preparations, phage cocktails, engineered phages, and phage-derived enzymes, has re-emerged as a potential option for difficult-to-treat and biofilm-associated infections in the context of rising antimicrobial resistance. Recent scientific and regulatory developments, such as the 2024 World Health Organization Bacterial Priority Pathogens List and the introduction of the European Pharmacopoeia general chapter 5.31 on phage therapy medicinal products, highlight the growing interest in establishing quality, safety, and governance standards for clinical implementation. This narrative review provides an overview of current clinical applications of phage therapy, drawing on published case reports, case series, early-phase clinical studies, and regulatory experiences across different healthcare settings. Clinical use has been reported in respiratory, urinary tract, musculoskeletal, cardiovascular, and device-associated infections, particularly in cases involving multidrug-resistant pathogens, often in combination with antibiotics. At the same time, the biological characteristics of phages, such as strain specificity, adaptive composition of phage cocktails, and the need for individualized formulations, pose significant regulatory and translational challenges. Access to phage therapy currently relies on heterogeneous regulatory mechanisms, including compassionate use programmes, magistral preparations, named-patient pathways, and other national frameworks. Overall, phage therapy represents a promising strategy for selected infections, but its broader clinical adoption will depend on harmonized regulatory approaches, robust quality standards, and the generation of stronger clinical evidence to support safe and scalable use.

Keywords:  antimicrobial resistance; bacteriophage; multidrug resistant pathogens; phage therapy; regulatory framework

DOI:  https://doi.org/10.3390/ph19010162
Antibiotics (Basel). 2026 Jan 04. pii: 55. [Epub ahead of print]15(1):

The Role of Genomics in Advancing and Standardising Bacteriophage Therapy.

Narina Abdraimova, Egor Shitikov, Maria Kornienko.

  Bacteriophage therapy, which employs bacterial viruses to selectively eliminate pathogenic bacteria, has re-emerged as a promising strategy in the face of increasing antimicrobial resistance. However, its widespread clinical implementation is constrained by concerns regarding safety, standardisation, and predictable efficacy. In this review, we examine the key role of genomics in transforming phage therapy from an empirical practice into a standardised and personalised modality of contemporary medicine. We describe how whole-genome sequencing (WGS) provides a basis for safety assessment by enabling systematic screening to exclude virulence factors, antibiotic resistance genes, and markers of lysogeny. WGS also facilitates the prediction of therapeutic efficacy and supports more rational phage selection by identifying receptor-binding proteins and characterising bacterial defence systems. In clinical settings, WGS data are increasingly used to monitor the evolution of bacterial populations and to adapt phage cocktails during treatment, thereby supporting personalised, adaptive phage therapy. Looking ahead, further progress is likely to come from integrating synthetic biology and artificial intelligence to engineer phage-based therapeutics with programmable specificity and predictable properties. Together, these developments are shaping a new paradigm of phage therapy as a scientifically grounded, standardised and controlled strategy to treat infections caused by antibiotic-resistant bacteria.

Keywords:  antimicrobial resistance (AMR); bacteriophage; genomics; personalised medicine; phage therapy; whole-genome sequencing (WGS)

DOI:  https://doi.org/10.3390/antibiotics15010055
Life (Basel). 2025 Dec 30. pii: 57. [Epub ahead of print]16(1):

Phage Therapy: Application and Related Problems-A Review.

Katharina Sippel, Branko Velimirov.

  Bacteriophages, viruses that target bacteria, offer a promising alternative to antibiotics in the face of escalating bacterial resistance. Despite their discovery over a century ago, their widespread adoption has been impeded by regulatory challenges, limited funding, and the dominance of antibiotics. This review evaluates the current status of phage therapy by examining a comprehensive literature search, applying predefined inclusion and exclusion criteria. The review assesses selected scientific reports and clinical studies for their safety and efficacy profiles. Our findings indicate that advancements in phage therapy involve critical steps such as rapid bacterial detection, effective isolation, production, purification of phage preparations, and understanding their interactions with the host. Clinical studies generally show promising safety profiles with fewer adverse events compared to controls, and some trials suggest efficacy even at lower phage titers. Case reports further highlight phage therapy's potential, demonstrating high success rates and minimal adverse events, although caution is advised due to potential biases. Despite promising results, significant research gaps remain, primarily due to the limited number of large-scale, well-designed clinical trials.

Keywords:  antibacterial agents; bacteriophage; case reports; clinical trials; innate and adaptive immunity; phage cocktails; safety; tolerability

DOI:  https://doi.org/10.3390/life16010057
Microorganisms. 2026 Jan 15. pii: 201. [Epub ahead of print]14(1):

Bacteriophage Therapy Against Klebsiella Pneumoniae.

Weijia Ding, Yicheng Wen, Liang Chen, Hong Du.

  Antibiotic resistance is arguably one of the greatest threats to global health today. The worldwide emergence of multidrug-resistant and hypervirulent Klebsiella pneumoniae underscores the urgent need for alternative treatments. Bacteriophages (phages) are considered one of the most promising alternatives to address this crisis. In this review, we summarize current knowledge of phage-host interactions and highlight recent advances in phage therapy against K. pneumoniae, including phage cocktails, antibiotic combination therapy, and treatments based on phage-derived proteins. Despite their tremendous therapeutic potential, significant challenges remain. We therefore also discuss strategies to optimize phage research and recent innovations in the field.

Keywords:  Klebsiella pneumonia; carbapenem resistant; hypervirulent; phage; phage therapy

DOI:  https://doi.org/10.3390/microorganisms14010201
BMJ Mil Health. 2026 Jan 27. pii: e003199. [Epub ahead of print]

Military health applications of bacteriophage: opportunities and challenges.

Nicola Reece, Scott J C Pallett, Lucy Lamb, Matthew K O'Shea, Katherine Clay.

  Bacteriophage (phage) is a virus that infects and kills bacteria but not human cells. As phages and bacteria have co-evolved over thousands of years, each phage is highly specific for its host bacteria. Phages were discovered over 100 years ago, with increasing antimicrobial resistance, there has been a resurgence of interest in phage therapy for antibiotic-resistant bacterial infections. Given their ubiquitous nature and high specificity, phages have many advantages as a potential therapy. However, their utility is not limited to treatment and phages can also be useful tools for diagnosis, decontamination and prophylaxis. This article reviews the potential uses for phage and explores the associated opportunities and challenges within a military medical context.

Keywords:  Microbiology; Military Personnel; Public health

DOI:  https://doi.org/10.1136/military-2025-003199
Antibiotics (Basel). 2026 Jan 09. pii: 75. [Epub ahead of print]15(1):

Pseudomonas aeruginosa Phage Cocktails: Rational Design and Efficacy Against Mouse Wound and Systemic Infection.

Mikeljon P Nikolich, Anna C Jacobs, Tracey L Peters, Yonas A Alamneh, Kirill V Sergueev, Nino Mzhavia, Chaselynn M Watters, Helen R Freyberger, Olga A Kirillina, Emily Engeman, Brett E Swierczewski, Mark P Simons, Schroeder M Noble, Damon W Ellison, Andrey A Filippov.

  Background/Objectives: Phages show efficacy against multidrug-resistant Pseudomonas aeruginosa, but limited host ranges require combining them in cocktails. In this work, we characterized 25 P. aeruginosa phages, developed therapeutic cocktails active against diverse clinical isolates, and tested phage efficacy in a mouse incisional wound model. Methods/Results: These phages represent seven genera, and genomic and phenotypic analyses indicate that 24/25 are lytic and suitable for phage therapy. Phage host ranges on a diversity panel of 156 P. aeruginosa strains that included 106 sequence types varied from 8% to 54%, and together the 24 lytic phages were active against 133 strains (85%). All of the phages reduced bacterial counts in biofilms. A cocktail of five lytic phages, WRAIR_PAM1, covered 56% of the strain panel, protected 100% of mice from lethal systemic infection (vs. 20% survival in the saline-treated group), and accelerated healing of infected wounds. An improved five-phage cocktail, WRAIR_PAM2, was formulated by a rational design approach (using phages with broader host ranges, more complementing activity, relatively low resistance background, and compatibility in mixes). Conclusions: WRAIR_PAM2 covered 76% of highly diverse clinical isolates and demonstrated significant efficacy against topical and systemic P. aeruginosa infection, indicating that it is a promising therapeutic candidate.

Keywords:  Pseudomonas aeruginosa; anti-biofilm effect; cocktail formulation; mouse wound model; multidrug resistance; phage compatibility; phage diversity; phage host range; phage receptors; phage resistance; phage therapy; phage treatment efficacy

DOI:  https://doi.org/10.3390/antibiotics15010075
Viruses. 2025 Dec 25. pii: 38. [Epub ahead of print]18(1):

The Forgotten History of Bacteriophages in Bulgaria: An Overview and Molecular Perspective on Their Role in Addressing Antibiotic Resistance and Therapy.

Nikolay Kalvatchev, Tannaz Khanbabapour, Arit Sakkeer, Iliya Tsekov, Yancho Delchev, Tanya Strateva.

  Bacteriophages, often referred to as "bacteria eaters," have gained renewed interest as a powerful alternative to traditional antibiotics, particularly in addressing antibiotic-resistant bacterial infections. The present review summarizes data collected in Bulgaria during the 1960s, 1970s, and 1980s, drawing connections between past findings and present-day understanding of cytotoxicity and the clinical validation of bacteriophage applications. Its sections describe phage structure, mechanisms of action, and historical findings both globally and within the Bulgarian context, while also highlighting emerging trends and applications. The cited studies delve into the past through contemporary research contributions related to "Bulgarian phages", a topic that remains underexplored in existing literature. The role of phages in medical microbiology is discussed alongside the challenges of therapeutic implementation, with particular focus on insights gained from the Bulgarian experience. In conclusion, by fostering international collaborations, investing in infrastructure, and establishing supportive policies, bacteriophage therapy can emerge as a critical tool for managing bacterial infections and reducing the global burden of antibiotic resistance in the future.

Keywords:  Bacteriophages; Bulgaria; antibiotic resistance; cytotoxicity; lytic activity

DOI:  https://doi.org/10.3390/v18010038
Appl Environ Microbiol. 2026 Jan 27. e0209525

Phage cocktails containing a dual-receptor Phikzvirus suppress resistance evolution in Pseudomonas aeruginosa.

Jumpei Fujiki, Kohana Tamamura, Keisuke Nakamura, Tomohiro Nakamura, Yoshiaki Sakata, Nana Kimura, Sayaka Ono, Nozomi Kojima, Keiko Inaba-Hasegawa, Michihito Sasaki, Masaru Usui, Tomohito Iwasaki, Hiroki Ando, Hirofumi Sawa, Hidetomo Iwano.

  While phage therapy is one of the promising strategies against antimicrobial resistant infections by Pseudomonas aeruginosa, the rapid emergence of phage-resistant variants remains a significant barrier to its long-term clinical efficacy, reflecting the constant evolutionary arms race between phages and their hosts. Here, we first characterized ΦBrmt, a Phikzvirus phage previously isolated from an LPS-defective P. aeruginosa mutant of the Pa12 strain. Whole-genome sequencing of ΦBrmt-resistant variants derived from the Pa12 strain (Pa12 mtΦBrmt) revealed mutations in genes for type IV pili and flagellar biosynthesis, resulting in decreased motility. To identify its receptors, we tested ΦBrmt against a panel of knock-out mutants, revealing that it failed to infect a ΔpilA/ΔfliC double mutant, despite being able to infect each single mutant. Transmission electron microscopy revealed that ΦBrmt adsorbed to the flagella of the Pa12 WT, whereas this adsorption was abolished on the phage-resistant mutants Pa12 mtΦBrmt. In contrast, Pbunavirus ΦS12-3 and ΦR26 were unable to infect the ΔgalU mutant but formed clear plaques on the ΔpilA and ΔfliC strains. A cocktail combining the pili/flagella-targeting ΦBrmt with an LPS-targeting Pbunavirus phage significantly suppressed the emergence of phage-resistant variants in vitro against representative clinical isolates when compared to single-phage treatments. Our findings demonstrate that combining phages targeting distinct classes of bacterial receptors is a powerful strategy to limit resistance development, indicating that identifying the receptor genes utilized by Pseudomonas phages can be the rational starting point for such design.IMPORTANCEPhage resistance limits the clinical efficacy of phage therapy against P. aeruginosa, a major antimicrobial-resistant pathogen. To address this, we demonstrate that a cocktail combining phages targeting distinct class of receptors effectively suppresses resistance. Through genetic analysis of resistant mutants, we first identified that the phage Brmt (ΦBrmt) uses both Type IV pili and flagella as receptors; a double mutant deficient in both pilA and fliC became completely resistant to infection. We then combined ΦBrmt with an LPS-targeting Pbunavirus phage, whose receptor was confirmed using a ΔgalU mutant. This receptor-diverse cocktail significantly suppressed the emergence of resistant variants across 10 diverse clinical isolates in vitro compared to single-phage treatments. These results underscore the importance of receptor-based molecular characterization as a critical first step in rational phage cocktail design. Our findings provide mechanistic insights into phage-host interactions and highlight a practical strategy for constructing receptor-diverse phage combinations to delay resistance evolution and enhance therapeutic robustness.

Keywords:  antimicrobial resistance (AMR); fitness; phage cocktail; phage resistance; phage therapy; trade-offs

DOI:  https://doi.org/10.1128/aem.02095-25
Viruses. 2026 Jan 09. pii: 92. [Epub ahead of print]18(1):

Feature-Based Growth Curve Classification Enables Efficient Phage Discrimination.

Yuma Oka, Keidai Miyakawa, Moe Yamazaki, Yuki Maruyama.

  Rapid isolation of therapeutic bacteriophages from environmental sources is essential for personalized phage therapy, particularly when appropriate phages are unavailable in existing banks. However, comprehensive characterization of all candidate phages is resource-intensive, especially when plaque morphologies are similar and fail to discriminate between distinct phages. Here, we present an upstream screening approach that utilizes co-culture growth curve analysis to rapidly triage phage isolates during the early isolation process. We extracted seven biologically meaningful features that capture lysis kinetics, lysis efficiency, and post-lysis dynamics from bacterial growth curves and applied unsupervised clustering algorithms for phage discrimination. Validation using T-phages at a multiplicity of infection of 0.01 demonstrated superior clustering performance (Adjusted Rand Index = 0.881 ± 0.057) compared to established metrics including the Virulence Index and Centroid Index. Application to phages isolated from sewage successfully identified all three genomically distinct species present (sampling score = 1.0), enabling targeted selection of representative phages for downstream characterization. This approach reduced candidates requiring detailed analysis by two-thirds (from 21 to 7 isolates) while maintaining complete species coverage, thereby providing an efficient and scalable screening tool that reduces workload for downstream analyses and accelerates discovery of novel therapeutic phages for clinical applications.

Keywords:  bacteriophage screening; growth curve analysis; phage therapy; unsupervised clustering

DOI:  https://doi.org/10.3390/v18010092
Zhonghua Yu Fang Yi Xue Za Zhi. 2026 Feb 06. 60(2): 270-276

[Advances in frontier technologies and innovative applications for the prevention and control of hospital infections associated with multidrug-resistant bacteria].

S Y Zhang, M Li.

Hospital-acquired infections (HAIs) significantly increase patient mortality and healthcare burden, with multidrug-resistant organisms (MDROs) exacerbating the challenge through diverse transmission routes, posing a global public health threat. Traditional control measures (e.g., hand hygiene, environmental disinfection, and antibiotic stewardship) remain central to HAI prevention but face technical and managerial limitations. Recent advances in novel technologies, including nanomaterials, phage therapy, and artificial intelligence, provide critical enhancements to existing control systems. This article systematically evaluates MDROs-related HAI control strategies and their clinical applications, proposing a future HAI prevention framework centered on technological precision, data integration, and dynamic adaptability.

DOI: https://doi.org/10.3760/cma.j.cn112150-20250331-00259
Bioengineering (Basel). 2025 Dec 31. pii: 51. [Epub ahead of print]13(1):

Understanding and Advancing Wound Healing in the Era of Multi-Omic Technology.

Serena L Jing, Elijah J Suh, Kelly X Huang, Michelle F Griffin, Derrick C Wan, Michael T Longaker.

  Wound healing is a complex, multi-phase process requiring coordinated interactions among diverse cell types and molecular pathways to restore tissue integrity. Dysregulation can lead to chronic non-healing wounds or excessive scarring, posing major clinical and economic burdens. Single-omics interrogate individual molecular layers, such as the genome, transcriptome, proteome, metabolome, or epigenome, and have revealed key cellular players, but provide a limited view of dynamic wound repair. Single-cell technologies provide higher resolution to single-omic data by resolving cell-type and state-specific heterogeneity, enabling precise characterization of cellular populations. Multi-omics integrates multiple molecular layers at single-cell resolution, reconstructing regulatory networks, epigenetic landscapes, and cell-cell interactions underlying healing outcomes. Recent advances in single-cell and spatial multi-omics have revealed fibroblast subpopulations with distinct fibrotic or regenerative roles and immune-epithelial interactions critical for re-epithelialization. Integration with computational tools and artificial intelligence (AI) continues to reveal cellular interactions, predict healing outcomes, and guide development of personalized therapies. Despite technical and translational challenges, including data integration and cost, multi-omics are increasingly shaping the future of precision wound care. This review highlights how multi-omics is redefining understanding of wound biology and fibrosis and explores emerging applications such as smart biosensors and predictive models with potential to transform wound care.

Keywords:  artificial intelligence; fibrosis; multi-omics; wound healing

DOI:  https://doi.org/10.3390/bioengineering13010051
J Appl Microbiol. 2026 Jan 28. pii: lxag025. [Epub ahead of print]

The Wound Microbiome in Chronic Wounds: A Biomarker and Therapeutic Target.

Bartosz Molasy, Małgorzata Wrzosek.

  Chronic wounds, including diabetic foot ulcers, venous leg ulcers, and pressure ulcers, remain a major global healthcare challenge, associated with substantial morbidity, risk of limb loss, and high healthcare costs. Increasing evidence indicates that the wound microbiome modulates inflammation, tissue repair, and responses to therapy, thereby influencing clinical outcomes. This review summarizes current knowledge on the composition and function of chronic wound microbial communities and discusses their clinical relevance as prognostic biomarkers and therapeutic targets. Microbiome structure is shaped by wound etiology, chronicity, anatomical site, and host comorbidities. Dysbiosis and biofilm formation contribute to persistent inflammation, antimicrobial tolerance, and delayed healing. Advances in sequencing and multi-omics technologies have improved microbial characterization and enabled the identification of candidate microbial signatures associated with healing trajectories. Emerging microbiome-modulating strategies such as probiotics, bacteriophages, topical oxygen approaches and nanotechnology-based interventions show potential to shift wound ecosystems toward a pro-healing state; however, robust clinical validation remains limited. Further clinical studies are needed to validate microbiome-guided diagnostics and interventions and to establish standardized protocols for their application in clinical practice.

Keywords:  antimicrobial resistance; bacteriophages; biofilm; chronic wound infections; probiotics; wound microbiome

DOI:  https://doi.org/10.1093/jambio/lxag025
Pharmaceuticals (Basel). 2025 Dec 27. pii: 61. [Epub ahead of print]19(1):

Salmonellosis as a One Health-One Biofilm Challenge: Biofilm Formation by Salmonella and Alternative Eradication Strategies in the Post-Antibiotic Era.

Michał Małaszczuk, Aleksandra Pawlak, Paweł Krzyżek.

  Non-typhoidal Salmonella (NTS) are globally distributed zoonotic pathogens of major concern within the One Health-One Biofilm framework. Fluoroquinolone-resistant Salmonella strains are included by the World Health Organization (WHO) in the Bacterial Priority Pathogens List as high-risk agents. A key virulence determinant of Salmonella is its ability to form biofilms, which may display multidrug-resistant (MDR) characteristics and contribute to bacterial persistence and treatment failure. Animals, particularly poultry and reptiles, represent important reservoirs of Salmonella, and reptile-associated salmonellosis (RAS) may manifest as extraintestinal infections in humans. In the post-antibiotic era, there is an urgent need to identify effective alternatives to conventional therapies. This review summarizes current knowledge on Salmonella biofilms, with particular attention to their MDR potential, and discusses possible strategies for their prevention and eradication, including specific immunoprophylaxis, bacteriophage therapy, and alternative antimicrobials. The promising antimicrobials include plant-based compounds/extracts, bacteriocins, fatty acids, and synthetic/semi-synthetic substances. The integration of vaccination, phage therapy, and novel anti-biofilm compounds may provide a sustainable alternative to antibiotics in controlling Salmonella infections and aligns with the principles of the One Health approach.

Keywords:  Salmonella; alternative therapies; biofilm; biofilm eradication; multidrug resistance; reptile-associated salmonellosis; zoonoses

DOI:  https://doi.org/10.3390/ph19010061
EXCLI J. 2025 ;24 1657-1689

Peptides in wound healing: A comprehensive review of their roles, challenges, and hydrogel-based delivery systems.

Rafl M Kamil, Shaik Nyamathulla, Syed Mahmood.

  Chronic wounds are characterized by prolonged healing durations and disrupted progression through the normal phases of wound healing, hemostasis, inflammation, proliferation, re-epithelialization and remodeling. These wounds are often complicated by persistent infections and underlying conditions like diabetic mellitus, which hinders effective tissue regeneration. Traditional dressings provide limited therapeutic benefits; therefore, recent advancements in wound care have introduced peptide-based therapies that have gained considerable attention for their multifunctional roles in modulating wound repair. Peptides possess intrinsic antimicrobial, anti-inflammatory, angiogenic, and pro-regenerative properties, enabling them to regulate diverse cellular and molecular events across all stages of healing. This review highlights the mechanistic roles of therapeutic peptides in regulating and orchestrating wound healing applications. We further classify bioactive peptides derived from microbial, animal, and plant sources with documented roles in wound healing, and also address synthetic peptides engineered for wound healing. We discussed the peptide-based hydrogels, recent advancements in peptide-based hydrogels in wound healing, and also those hydrogels that are currently under investigation in clinical trials. The primary objective of this review is to provide the readers a detailed overview of the advancements in wound healing studies especially peptide incorporated hydrogels. See also the graphical abstract(Fig. 1).

Keywords:  biomaterials; hydrogels; peptides; tissue regeneration; wound healing

DOI:  https://doi.org/10.17179/excli2025-8778
Front Microbiol. 2025 ;16 1726803

Two virulent bacteriophages targeting carbapenem-resistant Raoultella planticola.

Cuong V Hoang, Jonathan Fan, Lauren Bhasin, Anthony Del Mundo, Vanessa Law, Dominic Nguyen, Suraj Ganiger, Ashley Mansour, Christi L McElheny, Yohei Doi, Olakunle I Olawole.

  Carbapenem-resistant Raoultella planticola (CRRP) is an emerging nosocomial pathogen with limited therapeutic options. Here, we describe the comparative characterization of two novel virulent bacteriophages, Macy and Sally, both isolated from the same soil microenvironment. Macy exhibits exceptional lytic potency, with a burst size of 8,375 PFU per infected cell, narrow host specificity, and pronounced biofilm-disrupting activity likely mediated by a putative depolymerase. In contrast, Sally displays a broader host range, infecting both R. planticola and R. ornithinolytica (including a clinical CRRP isolate), while maintaining moderate lytic activity, notable acid tolerance, and substantial biofilm reduction. SNP analysis revealed that resistant isolates carried mutations in genes linked to surface polysaccharide biosynthesis and LysR-family transcriptional regulation, conferring resistance at a measurable cost to bacterial growth fitness. Genomic and phylogenomic analyses further revealed distinct evolutionary trajectories: Macy is a large (147.8 kb) member of Straboviridae Straboviridae with a mosaic genome related to Raoultella phages, whereas Sally is a compact (48.5 kb) Casjensviridae phage that is siphovirus more closely aligned with Klebsiella and Enterobacter phages. Pangenomic comparisons highlighted Macy's strain-specific gene expansions versus Sally's cross-genus homology, emphasizing divergent adaptation strategies. Together, these findings illustrate the complementary therapeutic potential of Macy and Sally and establish a genomic and phenotypic foundation for developing effective phage cocktails against multidrug-resistant Raoultella infections.

Keywords:  bacteriophage therapy; carbapenem-resistant Raoultella planticola; clinical strains; host range; multidrug-resistant pathogens

DOI:  https://doi.org/10.3389/fmicb.2025.1726803
Viruses. 2025 Dec 29. pii: 49. [Epub ahead of print]18(1):

Special Issue: "Bacteriophages and Biofilms 2.0".

Zuzanna Drulis-Kawa, Tomasz Olszak.

The natural ability of certain bacterial species to form biofilms presents numerous challenges for modern medicine and the food and pharmaceutical industries [...].

DOI: https://doi.org/10.3390/v18010049
Antibiotics (Basel). 2026 Jan 01. pii: 32. [Epub ahead of print]15(1):

Randomized, Negative-Controlled Pilot Study on the Treatment of Intramammary Staphylococcus aureus Infections in Dairy Cows with a Bacteriophage Cocktail.

Volker Krömker, Stefanie Leimbach, Anne Tellen, Nicole Wente, Janina Schmidt, Hansjörg Lehnherr, Franziska Nankemann.

  Background/Objectives: Staphylococcus (S.) aureus is a major pathogen causing bovine mastitis and is often refractory to antibiotic therapies due to virulence factors and resistance mechanisms. In this pilot study, the safety and efficacy of an intramammary phage cocktail, in naturally S. aureus-infected dairy cows, were investigated. Methods: The initial part of the study on farm 1 confirmed tolerability and safety, as there were no observed systemic side effects of treatment. The subsequent efficacy study on farm 2 included 23 with S. aureus infected udder quarters, which were randomly divided into a treatment group (n = 16) and a control group (n = 7). The quarters in the treatment group received five intramammary infusions of the phage cocktail at 12-h intervals. Results: This resulted in a bacteriological cure rate of 81.3% (13/16) for the treatment group, compared to 28.6% (2/7) in the control group (p = 0.026). Conclusions: These results indicate that phage therapy is well-tolerated and may be a promising alternative to antibiotics for treating S. aureus mastitis, although confirmation in larger-scale, multicenter studies is required.

Keywords:  S. aureus; bacteriophages; intramammary infection; mastitis; therapy

DOI:  https://doi.org/10.3390/antibiotics15010032
Adv Protein Chem Struct Biol. 2026 ;pii: S1876-1623(25)00085-9. [Epub ahead of print]149 245-311

Bacteriophage endolysins: A promising therapeutic strategy against drug- resistant Staphylococcus aureus.

Niranjana Rajesh, Jaya Bisht, Thulasi Sunilkumar, Alana Sibi, Dileep Francis.

  Staphylococcus aureus infections are difficult to treat due to the widespread emergence of antibiotic resistant strains, complex virulence mechanisms, and the ability to form recalcitrant biofilms. Infections with multi-drug resistant variants such as the methicillin resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) lead to increased morbidity and mortality and result in higher treatment cost compared to those with sensitive strains. While vaccines are sought as a preventive strategy, a clinically viable vaccine has not surfaced yet. Considering the rapid dissemination of resistant strains across the globe, the World Health Organisation has categorised S. aureus as an ESKAPE pathogen that requires the immediate development of alternative therapeutics. One of the most promising alternative to conventional antibiotics are bacteriophage endolysins, a family of peptidoglycan hydrolases capable of destabilising the peptidoglycan cell wall in bacteria by cleaving essential bonds in the peptidoglycan structure. Bacteriophages employ these for lysing the host cell during the last stage of their lytic life cycle to release progeny virions. A study published in 2001 demonstrated that purified endolysins can lyse bacterial cells rapidly and effectively when administered exogenously. Endolysins offer many advantages over conventional antibiotics: they are not likely to develop resistance as they target a highly conserved and indispensable component of the bacterial cell wall; they act faster than conventional antibiotics; they are species-selective in their lytic activity, sparing non-target organisms. Despite the numerous challenges in their clinical deployment, a large number of phage endolysins have been studied for their antibacterial potential against bacterial pathogens, including S. aureus. The present chapter provides a comprehensive account of the various endolysins, natural and engineered, studied as antimicrobial agents against drug resistant S. aureus.

Keywords:  Alternative therapeutics; Antimicrobial resistance; Bacteriophage endolysins; Exebacase; MRSA; Peptidoglycan hydrolases; Staphylococcus aureus

DOI:  https://doi.org/10.1016/bs.apcsb.2025.09.001
Small. 2026 Jan 29. e10741

AIEgen-Based Photothermal Nanoparticles With Dual Antibacterial and Anti-Inflammatory Activities for Enhanced Healing of Infected Diabetic Wounds.

Liwen Chen, Dawei Liang, Yiliang Qin, Lige He, Shuxian Li, Mengyi Cai, Yilan Tan, Jingjing Liang, Zhili Li, Lei Zheng, Jing Zhang, Mengchen Zou.

  Diabetic foot ulcers (DFUs) complicated by multidrug-resistant (MDR) bacterial infection present a significant clinical challenge that necessitates innovative therapeutic strategies. Conventional antimicrobial treatments often fail because of limited tissue penetration, antibiotic resistance, and poor efficacy against biofilm-forming pathogens. In this study, we developed a near-infrared (NIR) light-responsive aggregation-induced emission luminogen (AIEgen) with high photothermal conversion efficiency, excellent photostability, and favorable biocompatibility. Upon NIR light activation, this AIEgen can induce localized hyperthermia capable of disrupting bacterial membranes and penetrating deep into infected tissues, thereby effectively eradicating the embedded MDR pathogens and resilient biofilms. The antibacterial efficacy of the AIEgen was validated against MDR clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). In vitro and in vivo evaluations confirmed the potent bactericidal activity, efficient biofilm disruption ability, and minimal cytotoxicity of the AIEgen. Notably, in a DFU infection model, AIEgen administration and NIR light exposure significantly accelerated wound healing by eliminating pathogens, suppressing inflammation, promoting M2 macrophage polarization, enhancing collagen deposition, and stimulating angiogenesis. In conclusion, this AIEgen-based photothermal system offers a noninvasive, biocompatible, and deeply penetrating antibacterial strategy for the treatment of chronic MDR infections in DFUs and has great potential for clinical translation.

Keywords:  aggregation‐induced emission; infected diabetic foot ulcers; multidrug‐resistant bacteria; photothermal therapy

DOI:  https://doi.org/10.1002/smll.202510741
Front Vet Sci. 2025 ;12 1697229

Comprehensive genome analysis uncovers the diversity of jumbo phages in the pig gut microbiome.

Chao Wei, Zhe Chen.

  Gut microbiome research has historically focused on bacterial communities. In contrast, the roles of viruses, especially jumbo phages, remain poorly understood. Jumbo phages are of major interest because their large genomes encode unique functions that can influence host metabolism and ecosystem dynamics. This study bridges this gap by identifying 1,545 jumbo phage genomes from 450 pig gut metagenomes. Using CRISPR spacer analysis, we predicted archaeal or bacterial hosts and reconstructed competitive phage networks within this ecosystem. Phylogenetic divergence combined with orthologous protein comparisons supported establishing 14 novel jumbo phage families. Functionally, 10 of these novel families encode auxiliary metabolic genes (AMGs) that enhance host metabolism alongside anti-defense systems including DNA methyltransferases, HNH endonucleases, and glycosyltransferases. Ecological interactions were further elucidated through co-abundance networks (n = 857 pairs) and CRISPR spacer matching (n = 425 pairs), revealing relationships between novel jumbo phages and other jumbo phages. Collectively, this work expands genomic resources for pig gut viromes and delivers new insights into jumbo phages' functional capabilities, host associations, and global prevalence.

Keywords:  jumbo phages; phage diversity; pig guts; potential ecological interactions; potential novel jumbo phage families

DOI:  https://doi.org/10.3389/fvets.2025.1697229
Front Microbiol. 2025 ;16 1719973

Phage therapy against methicillin-resistant Staphylococcus pseudintermedius: a novel strategy for canine pyoderma.

Xiancheng Feng, Qingjie Du, Keyi Wang, Ruiqi Chen, Rui Ma, Yunping Xing, Xinyue Lei, Miao Wang, Pengxiu Dai, Xinke Zhang.

   Introduction: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) poses a major public health challenge due to its multidrug resistance. Phages represent an innovative therapeutic strategy with considerable potential against drug-resistant bacterial infections.
Methods: In this study, dogs clinically diagnosed with pyoderma were recruited to establish an epidemiological dataset, and multidrug-resistant S. pseudintermedius strains (including 6 MRSP isolates) were obtained from bacterial cultures. Three high-efficiency lytic phages were isolated using these MRSP strains as hosts and characterized. The combined efficacy of phages and antibiotics was evaluated in a pyoderma model via clinical scoring, histopathological examination, and tissue bacterial load quantification.
Results: Notably, these phages enhanced MRSP susceptibility to antibiotics, with genomic and proteomic analyses identifying key mediators of phage-mediated S. pseudintermedius lysis. The phage-antibiotic combination exhibited the most significant therapeutic effect on pyoderma, followed by the phage-only group. In contrast, the antibiotic-only group showed no significant improvement compared to the control group, with both yielding poor outcomes.
Discussion: This study provides a promising therapeutic strategy for the clinical management of canine pyoderma in veterinary medicine and offers valuable insights for safeguarding public health security.

Keywords:  methicillin-resistant Staphylococcus pseudintermedius; multidrug resistance; phages; pyoderma; therapy

DOI:  https://doi.org/10.3389/fmicb.2025.1719973
Medicina (Kaunas). 2026 Jan 13. pii: 163. [Epub ahead of print]62(1):

Mechanisms of Pseudomonas aeruginosa Resilience Against Antibiotic Treatment and Outlooks of Emerging Treatment Strategies.

Angelika Krūmiņa, Indra Zeltiņa, Paula Simsone, Emile Eulitz, Aigars Reinis, Ludmila Vīksna.

  Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa's resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority.

Keywords:  Pseudomonas aeruginosa; combination therapy; difficult-to-treat resistant (DTR) P. aeruginosa; emerging treatment; multidrug resistant P. aeruginosa; non-antibiotic therapies; novel antibiotics

DOI:  https://doi.org/10.3390/medicina62010163
Medicina (Kaunas). 2026 Jan 04. pii: 109. [Epub ahead of print]62(1):

Comparative Evidence on Negative Pressure Therapy and Hyperbaric Oxygen Therapy for Diabetic Foot Ulcers: A Systematic Review of Independent Effectiveness and Clinical Applicability.

Álvaro Astasio-Picado, Jesús Jurado-Palomo, Belén Pozo-Aranda, Paula Cobos-Moreno.

  Background and Objectives: To evaluate and synthesize evidence on the independent clinical effectiveness, safety, and applicability of Negative Pressure Wound Therapy (NPWT) and Hyperbaric Oxygen Therapy (HBOT) in diabetic foot ulcers (DFUs), and to determine whether current evidence allows for a direct comparison between both interventions: NPWT and HBOT are widely advanced therapies for DFUs. Although both show benefits, the relative superiority of one over the other remains unclear. Systematic review of the literature conducted in accordance with PRISMA guidelines. Materials and Methods: A comprehensive literature search was performed using two electronic databases. The review included randomized controlled trials, systematic reviews, meta-analyses, and non-randomized studies. Methodological quality and risk of bias were assessed using validated tools: RoB 2.0 for randomized trials, AMSTAR-2 for systematic reviews, and ROBINS-I for non-randomized studies. Results: A total of 22 studies were included. NPT was shown to be effective in accelerating wound healing, though results varied depending on the type of intervention and clinical context. HBOT demonstrated beneficial effects on angiogenesis and significantly reduced the rate of major amputations. Both therapies presented significant advantages in the management of diabetic foot ulcers. Conclusions: Negative pressure therapy and hyperbaric oxygen therapy are both effective treatments for diabetic foot ulcer healing. However, treatment selection should be individualized based on patient-specific clinical factors, ulcer severity, and available healthcare resources. Integrating these advanced therapies within a multidisciplinary care approach may optimize outcomes and reduce the risk of complications. Future research should include standardized, head-to-head RCTs.

Keywords:  amputation prevention; diabetic foot ulcer; hyperbaric oxygen therapy; negative pressure therapy; wound healing

DOI:  https://doi.org/10.3390/medicina62010109
Front Vet Sci. 2025 ;12 1748968

Microbial therapeutics for canine periodontal disease: current status and future perspectives.

Seok Bin Yang, Ji-Hoi Moon.

  Periodontal disease in dogs arises from ecological disruption of the oral microbiome. Sequencing-based studies and quantitative molecular analyses reveal characteristic dysbiotic transitions in affected dogs, with coordinated increases in Porphyromonas gulae, Prevotella, and Treponema, along with Treponema denticola and Tannerella forsythia, together with a loss of commensal-dominated genera such as Moraxella, Capnocytophaga, and members of the Neisseriaceae family. Rather than being driven by a single dominant pathogen, accumulating evidence indicates that canine periodontitis is driven by polymicrobial synergy within dysbiotic biofilms. This ecological perspective has stimulated growing interest in microbial therapeutics aimed at modulating community structure and function instead of relying solely on broad-spectrum antibiotics. Probiotics and postbiotics show potential in reducing halitosis and modulating epithelial innate immune responses. Bacteriophage-based approaches and predatory bacteria exhibit strain-specific antimicrobial activity in preclinical human or in vitro models, although their relevance to canine oral disease remains unvalidated. Synthetic biology and CRISPR-based antimicrobial systems provide conceptual frameworks for genotype-targeted modulation of virulence. Remaining challenges include transient microbial persistence, limited veterinary clinical evidence, biosafety concerns, and the absence of standardized regulatory pathways. Collectively, emerging microbial therapeutics highlight the potential but also the current limitations of ecology-guided, non-antibiotic strategies for canine periodontal therapy.

Keywords:  canine periodontal disease; microbial therapeutics; oral microbiome; probiotic and postbiotic therapy; synthetic biology

DOI:  https://doi.org/10.3389/fvets.2025.1748968
Pathogens. 2026 Jan 16. pii: 99. [Epub ahead of print]15(1):

Phage PM16 Therapy Induce Long-Term Protective Immunity Against Proteus mirabilis via Macrophage Priming.

Lina Al Allaf, Anton V Chechushkov, Vera V Morozova, Yulia N Kozlova, Tatiana A Ushakova, Nina V Tikunova.

  Bacteriophages, traditionally viewed solely as antibacterial agents, are increasingly being studied for their immunomodulatory properties. In this study, we demonstrate that PM16 phage therapy not only effectively controls subcutaneous Proteus mirabilis infection in mice but also induces long-term specific humoral immunity against subsequent reinfection. This immunomodulatory effect was dose-dependent. In vitro, PM16 directly activates macrophages, leading to increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and inducible nitric oxide synthase, and enhances macrophage bactericidal activity against P. mirabilis. We assume that the enhancement of the adaptive immune response is mediated not by the phage acting as a classical antigenic adjuvant but by its ability to prime innate immune cells, specifically macrophages. This priming leads to more efficient bacterial clearance, antigen presentation, and the formation of protective immunological memory.

Keywords:  PM16; Proteus mirabilis; bacteriophage; cytokines; humoral immunity; macrophage; phage therapy

DOI:  https://doi.org/10.3390/pathogens15010099
Curr Drug Discov Technol. 2026 Jan 20.

Cyclic Peptides in Wound Hydrogels: Current Advances and Future Directions.

Shahjad, Yashika Garg, Arun Kumar, Neha Pathak, Bhumika Chauhan, Sisir Nandi.

   INTRODUCTION: Chronic wounds, including diabetic foot ulcers and pressure ulcers, are significant clinical challenges due to impaired healing caused by chronic inflammation, poor angiogenesis, and Extracellular Matrix (ECM) abnormalities. These wounds impose a substantial socio-economic burden worldwide, necessitating innovative therapeutic strategies. This review explores the integration of cyclic peptides into hydrogel dressings as an advanced approach to improve wound healing outcomes, particularly in chronic wounds unresponsive to traditional treatments.
METHODS: The study looks at several strategies for integrating cyclic peptides into hydrogel matrices, including physical entrapment, covalent conjugation, self-assembly, layer-by-layer assembly, and microencapsulation. It also examines preclinical and clinical evidence supporting the effectiveness of cyclic peptide-loaded hydrogels in wound healing.
RESULTS: Cyclic peptide-loaded hydrogels demonstrate enhanced biological activity compared to linear peptides, exhibiting superior stability, membrane permeability, receptor binding affinity, and reduced immunogenicity. These hydrogels provide multifaceted therapeutic effects, including antimicrobial activity, modulation of inflammation, promotion of angiogenesis, ECM remodeling, and enhanced re-epithelialization. Preclinical models, including diabetic, septic, burn, and ischemic wounds, show accelerated healing, reduced bacterial load, and improved tissue regeneration.
DISCUSSION: Early clinical studies report significant reductions in healing times and increased wound closure percentages. Controlled release systems enable fine-tuning of peptide delivery to match the needs of the wound microenvironment. Despite promising results, issues such as peptide stability, scalable manufacturing, regulatory complexity, and production costs must be addressed before wider clinical adoption. The paper highlights emerging technologies like stimuli-responsive hydrogels, designer cyclic peptides, integration with cell therapies, wearable sensor platforms for real-time monitoring, and 3D bioprinting for personalized wound dressings. Mechanistic studies and precision medicine approaches are encouraged to optimize therapeutic efficacy.
CONCLUSION: The combination of cyclic peptides and hydrogel technology is a potential strategy for increasing wound healing, especially for chronic wounds that do not heal with standard methods. However, stability, manufacturing, and regulatory issues must be overcome before widespread clinical use can occur. Future research directions include personalized approaches, integration with cell therapies, and mechanistic studies to improve the efficacy of these wound-healing systems.

Keywords:  ECM; Wound healing; antimicrobial; cyclic peptides.; hydrogels

DOI:  https://doi.org/10.2174/0115701638416002251126071556
Antibiotics (Basel). 2026 Jan 04. pii: 54. [Epub ahead of print]15(1):

Nitric Oxide-Releasing Gels in the Context of Antimicrobial Stewardship, Biofilm Management, and Wound-Repair Biology.

Simon J L Teskey, Lisa Khoma, Michelle Lorbes, Chris C Miller.

  Topical antibiotics have long been used for the prevention and treatment of superficial skin and soft tissue infections; however, increasing evidence indicates that their clinical value is undermined by rising antimicrobial resistance, high rates of allergic sensitization, inadequate activity against biofilms, and a lack of wound-healing properties. Agents such as bacitracin, neomycin, polymyxin B, mupirocin, and fusidic acid act through narrow, target-specific mechanisms that facilitate resistance selection and provide limited benefit in chronic or polymicrobial wound environments. Contemporary antimicrobial stewardship frameworks therefore discourage routine use of topical antibiotics and increasingly favor non-antibiotic antiseptics with broad-spectrum activity and low resistance risk, including silver, iodine, polyhexamethylene biguanide, octenidine, and medical-grade honey. These modalities, however, primarily serve to reduce microbial burden and do not directly address the underlying biological impairments that prevent healing. Nitric oxide-releasing gels (NORGs) represent a novel class of topical antimicrobials that combine multi-target bactericidal activity with physiologic pro-healing effects. Nitric oxide exerts potent antimicrobial and antibiofilm effects via oxidative and nitrosative stress, disruption of metabolic pathways, inhibition of DNA replication, and interference with quorum sensing. Simultaneously, nitric oxide enhances angiogenesis, modulates inflammation, improves microvascular perfusion, and promotes fibroblast and keratinocyte function. Preclinical models and early-phase clinical studies demonstrate broad-spectrum efficacy-including activity against multidrug-resistant organisms-with favorable tolerability and minimal risk of resistance development. Although the current evidence base remains preliminary, NORGs offer a promising antimicrobial platform with the potential to reduce reliance on topical antibiotics while simultaneously addressing key barriers to wound healing. Larger randomized controlled trials, direct comparisons with established advanced dressings, and robust pharmacoeconomic evaluations are needed to define their optimal role within stewardship-aligned wound-care practice.

Keywords:  antimicrobial resistance; biofilm; general dermatology; medical dermatology; nitric oxide-releasing gel; skin infection; surgery; topical antibiotics; wound healing

DOI:  https://doi.org/10.3390/antibiotics15010054
Folia Microbiol (Praha). 2026 Jan 26.

Novel Koutsourovirus phages disrupt clinical multidrug-resistant Enterobacter cloacae biofilms: genomic and functional characterization.

Ibtihadj Souda, Karima Boubekri, Hibat Ellah Boutadjine, Amal Thebti, Hadda Imene Ouzari, Benjamin D Hatton, Dalal Asker.



Keywords:   Koutsourovirus ; Bacteriophage therapy; Biofilm disruption; Depolymerase; Multidrug-resistant Enterobacter cloacae

DOI:  https://doi.org/10.1007/s12223-026-01424-2
ACS Sens. 2026 Jan 28.

The Overlooked Power of Targeted Phage Lysis in Bacterial Biosensing.

Hannah Mann, Akansha Prasad, Fereshteh Bayat, Carlos D M Filipe, Zeinab Hosseinidoust, Tohid F Didar.

  Cell lysis to release intracellular targets is a vital step in many bacterial sensing platforms and is often achieved through chemical or physical approaches. However, these conventional methods can have certain limitations such as cost, required equipment, safety, or risk of target damage. Cell lysis induced by bacteriophages, which are bacteria-infecting viruses, has some notable advantages, including safety and the self-amplifying properties of phage. Bacteriophages also induce species-selective infection, enabling the targeted lysis of a specific bacterial species in mixed cultures. Despite this, bacteriophage-induced lysis has to date been relatively poorly adopted in the bacterial biosensing field. In this Perspective, we outline the potential benefits of bacteriophage lysis in biosensors, while also exploring the reasons that it has not been more widely adopted. We also identify future research directions to facilitate increased incorporation of bacteriophages into bacterial detection platforms, including improving the characterization, availability, and stability of phage strains.

Keywords:  bacteriophage; biosensing; cell lysis; clinical diagnostics; contamination sensing; pathogen detection

DOI:  https://doi.org/10.1021/acssensors.5c03683
Nucleic Acids Res. 2026 Jan 22. pii: gkag066. [Epub ahead of print]54(3):

Mycobacterial non-homologous end joining is required for antiphage defense.

Yu Huang, Hongxiang Xu, Tianyu Zhang, Yiran Liao, Jiayue Hu, Zibei Huang, Huifan Hu, Peibo Li, Lin Fan, Jianping Xie.

In the ongoing arms race with phages, bacteria have evolved diverse defense systems, such as CRISPR-Cas and restriction-modification systems. The DNA double-strand break repair system represents a core mechanism for maintaining genomic integrity and is vital for cell survival. However, it remains unknown whether and how these repair systems contribute to phage resistance. This study systematically investigates the role of the non-homologous end joining (NHEJ) during phage infection in Mycobacterium smegmatis. We found that NHEJ deficiency compromises host resistance to phage SWU1, as evidenced by increased plaque counts and reduced bacterial survival. Mechanistically, phages exploit host NHEJ for genomic repair; however, the error-prone nature of NHEJ leads to imperfect repair at phage cos sites, thereby blocking replication. The host modulates the balance between NHEJ and homologous recombination (HR) to control repair fidelity: NHEJ loss shifts the balance toward high-fidelity HR, which in turn promotes phage survival. Furthermore, NHEJ deficiency exacerbates infection-induced oxidative stress, leading to a compromise in bacterial viability. Our findings reveal the multifaceted functions of NHEJ in mycobacterium-phage interactions and provide new insights into how DNA repair systems shape antiphage defense and coevolution.

DOI: https://doi.org/10.1093/nar/gkag066
Br J Hosp Med (Lond). 2026 Jan 19. 87(1): 50163

The Airway Microbiome in Chronic Obstructive Pulmonary Disease (COPD): A Guide for Clinicians.

Wei Ling Yolanda Koo, Kai Xian Thng, Pei Yee Tiew, Sanjay H Chotirmall.

  Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory condition marked by chronic symptoms and frequent exacerbations, contributing to significant morbidity and mortality. The advent of molecular microbiology and next-generation sequencing (NGS) has expanded our understanding of the lung microbiome, and integration of microbiome datasets with other omics reveals important microbial-metabolic-immuno-inflammatory interactions that influence COPD pathogenesis. Recent studies have highlighted dysbiosis of the airway microbiome, with shifts in bacterial, viral, and fungal communities playing a crucial role in disease progression, exacerbations and clinical outcomes. Moreover, microbiome changes are observed in COPD associated overlap syndromes, complicating diagnosis and treatment. This review synthesizes current microbiome research in COPD, focusing on its clinical relevance, including its potential as a diagnostic and prognostic tool. We additionally discuss the challenges of integrating microbiome data into clinical practice, emphasizing the need for personalized, precision medicine approaches to optimize COPD management and improve patient outcomes.

Keywords:  COPD; metagenomic; microbiome; mycobiome

DOI:  https://doi.org/10.31083/BJHM50163
Int J Mol Sci. 2026 Jan 18. pii: 944. [Epub ahead of print]27(2):

Therapeutic Potential of a Novel Stenotrophomonas maltophilia Phage XAN_XB1: Isolation, Characterization, Genome Analysis and Evaluation in Mice Model.

Qingqing Yang, Baoyu Gan, Zhonglin Wang, Shan Jiang, Cao Qiu, Yawen Wang, Bing Liu, Xiaoyan Zeng.

  A novel lytic bacteriophage, XAN_XB1, was isolated from hospital wastewater through host bacterial enrichment and evaluated for its potential in controlling multidrug-resistant Stenotrophomonas maltophilia infections. Transmission electron microscopy revealed that XAN_XB1 has a long tail, possessing an icosahedral head of ~80 nm in diameter and a tail measuring ~150 nm in length. It produced clear plaques of 0.5-1 mm on host bacterial lawns. Host range analysis demonstrated its ability to infect multiple multidrug-resistant S. maltophilia isolates. Biological characterization showed that the phage is chloroform-insensitive, retains strong lytic activity across a wide temperature (4-60 °C) and pH (3.0-10.0) range, and achieves more rapid host suppression under higher multiplicity of infection (MOI). Whole-genome sequencing determined a ~47 kb double-stranded DNA genome encoding 71 predicted open reading frames, with no known virulence or antibiotic resistance genes. Phylogenetic analysis of MCP and terminase large subunit sequences placed XAN_XB1 in a unique Caudoviricetes, with ANI values below the 95% ICTV threshold verifying its status as a novel phage species. The XAN_XB1 therapy significantly alleviates S. maltophilia infection-induced severe pulmonary inflammatory lesions, high mortality, elevated serum inflammatory factors and massive pulmonary bacterial colonization in male BALB/c mice, confirming its favorable therapeutic effect on such infections. Collectively, these results reveal that is an efficacious candidate for therapeutic development against S. maltophilia infections.

Keywords:  Stenotrophomonas maltophilia; bacteriophage; drug-resistant bacteria; phage therapy

DOI:  https://doi.org/10.3390/ijms27020944
Pediatr Pulmonol. 2026 Jan;61(1): e71470

Exploring Exercise as Airway Clearance in Cystic Fibrosis: A Qualitative Study From the ExACT-CF Feasibility Trial.

ExACT‐CF study group

   QUESTION: Cystic fibrosis (CF) affects > 11,300 people in the UK and is characterized by thick, sticky mucus in the lungs, leading to recurrent infections, inflammation, and progressive respiratory decline. Chest physiotherapy remains a cornerstone of airway clearance; however, many people with CF (pwCF) find it burdensome and time-consuming. Exercise has been proposed as a potentially effective and more acceptable alternative. The ExACT-CF feasibility trial evaluated the use of exercise as an airway clearance technique in pwCF on modulator therapy.
METHODS: This nested qualitative study explored the experiences of participants and healthcare professionals involved in the ExACT-CF trial, alongside broader perspectives on airway clearance, to inform future research and clinical practice. Purposively sampled semi-structured interviews were conducted with 32 individuals: ten pwCF, five parents, twelve healthcare professionals, four decliners, and one participant who withdrew. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically using "The Framework Method."
RESULTS: Two primary themes emerged. Theme 1 reflected experiences and lessons learned from the trial, including reported barriers and facilitators around recruitment, randomization, and daily implementation. Despite some minor difficulties, trial participation, processes, and the intervention itself were broadly acceptable. Theme 2 highlighted a preference for using ExACT alone or interchangeably with chest physiotherapy. Participants emphasized the need for robust clinical evidence to guide use.
ANSWER: This study highlights the acceptability of both the ExACT-CF trial processes and the use of this exercise-based airway clearance technique. Findings support progression to a definitive trial and further exzploration of patient-centered, flexible approaches to airway clearance in CF.
TRIAL REGISTRATION: NCT02429180.

Keywords:  chest physiotherapy; cystic fibrosis; physical activity; qualitative; semi‐structured interviews

DOI:  https://doi.org/10.1002/ppul.71470
Expert Rev Anti Infect Ther. 2026 Jan 30.

How ready are we to use artificial intelligence in our fight against Antimicrobial resistance? An ESGAID and EAAS perspective.

Daniele Roberto Giacobbe, Rafi Ahmad, Fatih Mehmet Akilli, Abdulaziz Ascandari, David W Eyre, Antonio Gallardo-Pizarro, Carolina Garcia-Vidal, Bruno Silvester Lopes, Ekaterina Lyutsova, Ruslan Rakhimov, Alberto Rizzo, Holger Rohde, Zahra Sadeghi, Valentijn Schweitzer, Ermira Tartari, Eva Torres-Sangiao, Alejandro Guerrero-López.

   INTRODUCTION: Antimicrobial resistance (AMR) remains one of the greatest threats to global health, requiring innovative approaches to antibiotic discovery, surveillance, diagnosis, and prescribing. In recent years, artificial intelligence (AI) has increasingly been applied across these domains, with the dual aim of accelerating research and strengthening antimicrobial stewardship.
AREAS COVERED: This perspective summarizes current advances and challenges in applying AI for tackling AMR. We examine the role of AI in antibiotic discovery, laboratory surveillance, diagnosis of resistant infections, and clinical decision support systems (CDSSs). Finally, we address the ethical and regulatory landscape, data transparency, and liability concerns.
EXPERT OPINION: AI offers unprecedented opportunities across the continuum of our efforts to counteract AMR, yet its adoption faces substantial hurdles. Some central challenges include the balance between model accuracy and explainability, the lack of widespread digital access, quality and transparency of training datasets, and usability for clinicians. Progress will depend on multidisciplinary collaboration, robust regulatory oversight, and the development of training programs equipping future healthcare professionals with AI-aware reasoning skills. Ultimately, AI should not replace but rather augment human reasoning in the fight against AMR, aligning innovation with ethical principles to ensure safer, more equitable AI-enhanced antibiotic prescribing and antimicrobial stewardship.

Keywords:  Antimicrobial resistance; accuracy; explainability; large language models; machine learning; multidrug resistance

DOI:  https://doi.org/10.1080/14787210.2026.2625382
Clin Microbiol Infect. 2026 Jan 22. pii: S1198-743X(26)00009-1. [Epub ahead of print]

The role of the gut microbiome in MDRO colonisation and infection.

Blair Merrick, Rebecca Cooper, Benjamin Davido, Simon Goldenberg.

BACKGROUND: Colonisation of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonisation resistance (CR) - the ability to prevent or limit the establishment of pathogens, including MDROs - through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures.
OBJECTIVES: To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonisation and infection, and to highlight implications for clinical practice, policy, and research.
SOURCES: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists.
CONTENT: CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, non-antimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonisation and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR - such as diet-based strategies, probiotics, and faecal microbiota transplant - show promise but require robust and repeated, context-specific evaluation.
IMPLICATIONS: Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.

DOI: https://doi.org/10.1016/j.cmi.2026.01.009
Dent Mater. 2026 Jan 23. pii: S0109-5641(26)00018-7. [Epub ahead of print]

Organ-on-a-chip in oral medicine: Emerging approaches and applications.

Fushuang Liu, Tianyi Wang, Yang Song, Yongwen Guo.

   OBJECTIVES: Organ-on-a-chip (OoC), as a highly biomimetic microphysiological system, is demonstrating significant potential in oral medicine research and clinical application. This review outlines the latest advances and specific applications of OoC in the field, with a focus on its value in emulating the complex oral microenvironment, facilitating the development of materials and drugs, and advancing personalized medicine. Furthermore, it discusses how emerging technologies such as artificial intelligence (AI) may contribute to the evolution of dentofacial OoCs.
DATA AND SOURCES: A review of literature was conducted through online databases, including PubMed, Google Scholar, Embase, Scopus, and Web of Science.
STUDY SELECTION: Studies were selected based on relevance, with a preference for research from the last 5 years.
CONCLUSIONS: This review concludes that the dentofacial tissues and their functions can be simulated via OoCs, including dentin, dental pulp, periodontal tissue, oral mucosa, and salivary glands. They hold significant value in modeling oral disease, evaluating oral restorative materials, studying head and neck tumor metastasis, and screening drugs. Furthermore, the integration with AI will enable intelligent acquisition and analysis of high-throughput, real-time dynamic data within the chips, assisting in their design and optimization, and promoting precise control of the microenvironment.

Keywords:  AI for prediction; Dentin; Disease modeling; Microenvironment simulation; Organ-on-a-chip; Personalized Medicine

DOI:  https://doi.org/10.1016/j.dental.2026.01.009
Pathogens. 2026 Jan 07. pii: 62. [Epub ahead of print]15(1):

Gut and Joint Microbiome and Dysbiosis: A New Perspective on the Pathogenesis and Treatment of Osteoarthritis.

Paulina Plewa, Patryk Graczyk, Karolina Figiel, Aleksandra Dach, Andrzej Pawlik.

  Osteoarthritis (OA) is one of the most common and burdensome musculoskeletal disorders and a major cause of pain, disability, and reduced quality of life worldwide. In recent years, increasing attention has been paid to extra-articular factors influencing its development and progression, opening new avenues of research into pathophysiological mechanisms and potential therapies. One of the most promising areas concerns the role of the gut-joint axis and related alterations in the gut microbiome. Numerous studies indicate that an imbalance of gut bacteria, increased intestinal permeability, and low-grade inflammation may contribute to the progression of degenerative joint processes. The mechanisms through which the microbiota influences the immune system and host metabolism are becoming increasingly well understood, including pathways involving short-chain fatty acids, tryptophan metabolites, and bile acids. Despite growing evidence linking dysbiosis to the pathogenesis of OA, effective therapeutic strategies based on microbiome modulation remain under active investigation. Among the most frequently studied approaches are probiotics, dietary interventions, and more advanced strategies such as gut microbiota transplantation and targeted modulation of microbial metabolites. However, before these methods can become part of routine treatment, extensive clinical trials and a clearer understanding of causal relationships between the microbiome and joint degeneration are required. This article summarises the current state of knowledge regarding the role of the gut microbiome in osteoarthritis, outlines key research findings, and highlights current and potential therapeutic directions.

Keywords:  bacteria; gut–joint axis; microbiome; osteoarthritis

DOI:  https://doi.org/10.3390/pathogens15010062