bims-fagtap 2025-09-14 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–09–14
25 papers selected by
Luca Bolliger, lxBio

Phage therapy in finfish aquaculture: how to get there?
The prospect of approved and commercially available phage therapeutics.
Phage therapy modulates the gut microbiome and immune responses in non-typhoidal Salmonella-induced colitis.
Bacteriophage-Based Approach Against Biofilm Infections Associated with Medical Devices: A Narrative Review of ESKAPE Pathogens.
Reprogramming resistance: phage-antibiotic synergy targets efflux systems in ESKAPEE pathogens.
Cross-border dialogue: An international survey of regulators on phage therapy.
Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health.
Overcoming Multi-Drug-Resistant Klebsiella pneumoniae Infections.
Phage-nanomaterial platforms for precision antimicrobial therapy: from design to therapeutic application.
Results of TOR001: an open-label single patient study using targeted bacteriophage therapy for the treatment of a chronic urinary tract infection.
New anti-infective approaches to treat airway infections in persons with cystic fibrosis and bronchiectasis.
Optimizing the Production of Therapeutic Bacteriophages Through Quality by Design: A Case Study on Pseudomonas Aeruginosa.
Quantifying phage infectivity from characteristics of bacterial population dynamics.
Bacteriophage therapy in dermatology: A systematic review.
Characterization of the novel Cutibacterium acnes phage KIT08 and its associated pseudolysogenic bacterial isolate.
Progressive Hydrogel Applications in Diabetic Foot Ulcer Management: Phase-Dependent Healing Strategies.
Characterization of phage vB_EfS_C1 and investigation of antibacterial and antibiofilm properties against vancomycin-susceptible and vancomycin-resistant Enterococcus faecium.
Environmental Application of a Bacteriophage Cocktail Reduces Antibiotic-Resistant Escherichia coli in Poultry Litter Without Disrupting Gut Microbiota.
Mesenchymal Stromal Cell Extracellular Vesicles Reduce Pseudomonas Biofilm Formation, and let-7b-5p Loading Confers Additional Anti-Inflammatory Effects.
A review of biomimetic hydrogel wound dressings: Design inspiration, construction strategies, multifunctionality and applications.
Infectious Keratitis Management: 10-Year Update.
Learning about break-induced replication from bacteriophages.
Pharmacological insights into gut microbiota modulation in systemic lupus erythematosus: Mechanisms, treatment strategies, and clinical implications.
Wound healing and signaling pathways.
Fundamentals of microbiome-based therapies for reproductive tract inflammatory diseases in domestic animals.

Trends Microbiol. 2025 Sep 08. pii: S0966-842X(25)00245-8. [Epub ahead of print]

Phage therapy in finfish aquaculture: how to get there?

Lotta A I Landor, Valeria Ruffo, Sachia J Traving, Mathias Middelboe.

  As antimicrobial resistance threatens the future of the aquaculture industry, numerous studies have investigated the use of phages against aquaculture diseases over the past decades. Despite reports of efficient pathogen control, commercial phage solutions are sparse. We discuss limitations of phage therapy and provide suggestions for the progression towards commercially viable solutions. We argue that phage therapy in aquaculture should focus on disease prevention rather than on treatment to reduce the need for antimicrobials. Further, the phage-delivery methods should target the variable pathogen distribution throughout the production chain. Finally, the key challenges of host-specificity and resistance should be tackled by developing predictive tools that can be used to assess phage-pathogen compatibility within a realistic timeframe.

Keywords:  fish pathogens; machine learning; phage applications; phage prediction; phage–host interactions

DOI:  https://doi.org/10.1016/j.tim.2025.08.002
Int J Antimicrob Agents. 2025 Sep 06. pii: S0924-8579(25)00167-0. [Epub ahead of print] 107612

The prospect of approved and commercially available phage therapeutics.

Harald König.

  As antibiotic resistance of bacterial pathogens spreads, interest in bacteriophage (phage) therapy has soared again in many countries. Currently, there is no phage therapeutic with marketing approval and phage treatments are relegated to few patients, mostly under compassionate use schemes when approved drugs failed or are unavailable. Commercially manufactured and approved phage preparations could both expand the availability of therapeutic phages for existing, exemptional treatment schemes and result in more broadly usable phage therapeutics with marketing authorization. The lack of clinical evidence from modern clinical trials and issues with the patenting of phages are often seen as important challenges toward commercially produced and approved therapeutic phages. Here, an analysis of available data suggests that while a surge in patent filings and new clinical trials by biotech companies has begun and these challenges may be surmountable, the long-term success of commercial phage therapeutics will hinge on policy solutions that address post-approval regulatory and economic barriers.

Keywords:  antibiotic resistance; clinical trials; marketing authorization; patents; phage therapy; regulatory and economic issues

DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107612
Food Res Int. 2025 Nov;pii: S0963-9969(25)01341-9. [Epub ahead of print]219 117003

Phage therapy modulates the gut microbiome and immune responses in non-typhoidal Salmonella-induced colitis.

Md Sharifull Islam, Ping Wei, Kaimin Zhang, Ishatur Nime, Fan Pan.

  Inflammatory bowel disease (IBD) encompasses two main conditions: Crohn's disease and ulcerative colitis. The role of foodborne pathogens, often transmitted through contaminated food, is a subject of ongoing research regarding their potential involvement in IBD. The most common foodborne pathogens S. typhimurium usually causes intestinal inflammation in the intestines of both humans and cattle, known as enterocolitis. Phage therapy shows promise in treating Salmonella-induced colitis due to its highly specific targeting of bacteria. Here, we demonstrated the efficacy of phage therapy in a murine model of Salmonella-induced colitis. In mice, Salmonella administration exacerbated colitis severity, as evidenced by reduced colon length and elevated production of inflammatory cytokines. Comprehensive metabolomic investigations demonstrated that treatment with a Salmonella-specific novel phage FPSP6 effectively mitigated colitis induced by Salmonella. This therapeutic approach effectively reduced intestinal inflammation, increased CD4+ T-cell levels and decreased cytokine expression, demonstrating its potential efficacy and safety for treating Salmonella-induced colitis. This study, the first to verify the effectiveness and immunomodulatory mechanism of FPSP6, indicates that phage therapy targeting the gut microbiota is a viable alternative to antibiotics, connecting phage therapy, immune regulation, and microbial dynamics in the context of intestinal inflammation caused by foodborne pathogens.

Keywords:  Colitis; Dysbiosis; Immune regulation; Phages; Therapeutic potential

DOI:  https://doi.org/10.1016/j.foodres.2025.117003
Int J Mol Sci. 2025 Sep 06. pii: 8699. [Epub ahead of print]26(17):

Bacteriophage-Based Approach Against Biofilm Infections Associated with Medical Devices: A Narrative Review of ESKAPE Pathogens.

Karolina Pawłuszkiewicz, Tomasz Busłowicz, Matylda Korgiel, Anita Faltus, Emilia Kucharczyk, Barbara Porębska, Paweł Pochciał, Natalia Kucharczyk, Emil Paluch.

  The increasing incidence of hospital-acquired infections and antimicrobial-resistant pathogens poses a major clinical challenge. Nearly all medical devices are vulnerable to bacterial biofilm formation, which acts as a protective coating against the host defense systems and antibiotics. The persistence of biofilm infections, accounting for around 65% of all microbial infections, and poor conventional treatment outcomes has driven interest in alternative approaches like bacteriophage therapy. This review encompasses key aspects of biofilm biology, taking into account the clinically significant ESKAPE pathogens, and provides an in-depth analysis of the role of phage agents in biofilm control as a new biofilm control strategy. Diving deeper into the mechanisms of phage-mediated processes, the review examines how bacteriophages penetrate and disrupt biofilm architecture and evaluates current therapeutic strategies that exploit these actions, acknowledging their limitations and considering possible future directions.

Keywords:  bacterial; bacteriophages; biofilms; drug resistance; health care associated infection; phage therapy

DOI:  https://doi.org/10.3390/ijms26178699
mBio. 2025 Sep 08. e0182225

Reprogramming resistance: phage-antibiotic synergy targets efflux systems in ESKAPEE pathogens.

Anita Tarasenko, Bhavya N Papudeshi, Susanna R Grigson, Vijini Mallawaarachchi, Abbey L K Hutton, Morgyn S Warner, Jeremy J Barr, Jon Iredell, Bart Eijkelkamp, Robert A Edwards.

  Multidrug-resistant (MDR) and extensively drug-resistant (XDR) ESKAPE pathogens pose a significant global health threat due to their ability to evade antibiotics through intrinsic and acquired mechanisms. These bacteria, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter species, evade antibiotics through intrinsic and adaptive mechanisms. Common strategies include capsule formation, biofilm, β-lactamase production, and efflux activity. Using these mechanisms, bacteria can evade the effects of antibiotics, leading to persistent and difficult-to-treat infections. Understanding the mechanisms of resistance is crucial in developing effective strategies to combat MDR and XDR ESKAPEE pathogens. A promising approach is the development of alternative treatments targeting specific resistance mechanisms in these pathogens. Bacteriophages (phages), which co-evolve with bacterial hosts, offer a dynamic therapeutic alternative by targeting pathogenic bacteria using precision-based strategies. This targeted approach can overcome antibiotic resistance and reduce the risk of damaging the beneficial microbiota. Phages can restore susceptibility in previously untreatable infections by enhancing antibiotic uptake and imposing fitness costs on resistant strains. However, therapeutic deployment faces challenges such as rapid evolution of phage resistance, inconsistent production standards, and limited regulatory pathways. This review examines the mechanistic insights into phage-antibiotic synergy, with a focus on efflux pump-mediated resistance. It discusses emerging therapeutic strategies, current clinical applications, and the translational frameworks needed to integrate phage therapy into mainstream medicine and transform the clinical management of drug-resistant ESKAPEE infections.

Keywords:  ESKAPEE pathogens; efflux pump inhibition; multidrug resistance (MDR); phage therapy; phage-antibiotic synergy

DOI:  https://doi.org/10.1128/mbio.01822-25
Int J Antimicrob Agents. 2025 Sep 06. pii: S0924-8579(25)00169-4. [Epub ahead of print] 107614

Cross-border dialogue: An international survey of regulators on phage therapy.

Riley D Alvarez, Christine Årdal, Annika Y Classen, Tobi E Nagel, Pieter-Jan Ceyssens, Greg J German.

  With antimicrobial resistance as a worldwide public health concern, bacteriophage (phage) therapy (PT) may help treat bacterial infections. However, given its particularities compared with traditional small molecule drugs, there are variations in how it is regulated worldwide. Regulators are key players governing PT, yet their perspectives have been largely unexplored. Here, we present findings from the first international survey aimed at capturing the current and future landscape of PT according to regulators. We distributed the survey to members of the second European Union-Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections and individually contacted regulators. Results were collected between October 30, 2024 and March 26, 2025. Twenty-three respondents represented twenty-one countries across Europe, North America, Africa, and Oceania (response rate 67%). Phages or PT were reported as being mentioned in only three national action plans (13%). Nearly half of the respondents declared no prior involvement in phage-related regulatory processes in the past decade, and 32% were uncertain if phages have ever been used therapeutically in their country. Among those who were aware of previous in-country PT, single-use cases dominated, with 27% of respondents acknowledging this as a resource burden (compared to other regulatory applications). Some regulators reported that adapted frameworks are being explored for PT, while one indicated a new framework was being considered. These results underscore that globally major steps aimed at increasing awareness, engagement, and collaboration on best practices amongst regulators are still required to clarify and improve clinical access pathways for PT.

Keywords:  Antimicrobial resistance; Bacteriophage; Phage therapy; Regulation; Survey

DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107614
Microb Pathog. 2025 Sep 04. pii: S0882-4010(25)00743-0. [Epub ahead of print]208 108018

Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health.

Jaishriram Rathored, Tanushree Budhbaware.

  Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies.

Keywords:  Antimicrobial peptides; Antimicrobial strategies; Bacteriophage therapy; CRISPR-Cas systems; Multidrug-resistant bacteria; Nanotechnology

DOI:  https://doi.org/10.1016/j.micpath.2025.108018
Microb Drug Resist. 2025 Sep 08.

Overcoming Multi-Drug-Resistant Klebsiella pneumoniae Infections.

Nastaran Javan, Reza Ghotaslou, Hossein Samadi Kafil, Mohammad Yousef Memar, Javid Sadeghi, Pardis Ghotaslou.

  Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR K. pneumoniae infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR K. pneumoniae infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant K. pneumoniae, AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR K. pneumoniae infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.

Keywords:  AMR; alternative treatments; multidrug-resistant Klebsiella pneumoniae

DOI:  https://doi.org/10.1177/10766294251375937
Nanoscale. 2025 Sep 11.

Phage-nanomaterial platforms for precision antimicrobial therapy: from design to therapeutic application.

Manlin Qi, Andy Tay.

The rapid increase in multidrug-resistant (MDR) bacteria and biofilm-associated infections has intensified the global need for innovative antimicrobial strategies. Phage therapy offers promising precision against MDR pathogens by utilizing the natural ability of phages to specifically infect and lyse bacteria. However, their clinical application is hampered by challenges such as narrow host range, immune clearance and limited efficacy within biofilms. Nanotechnology has emerged as a powerful complementary approach, offering broad-spectrum antimicrobial properties, tunable physical properties and responsive functionality. Despite these advantages, most nanomaterials lack precise bacterial targeting and may pose biosafety risks. The combination of phages and nanomaterials opens new avenues for synergistic antibacterial therapy. Nanomaterials not only enhance phage stability, delivery and penetration, but also enable multimodal therapy, including photothermal and photodynamic therapy. At the same time, phages endow nanomaterials with highly specific bacterial recognition and lysis activities, improving therapeutic selectivity and reducing microbiota destruction. In this paper, we review the structural features of phages, strategies to construct phage-nanomaterial platforms, the antimicrobial mechanisms of nanomaterials and their applications in different infection models. We also highlight current limitations and future directions. Together, these insights provide a foundation for the rational design of next-generation antimicrobial platforms for precision therapy.

DOI: https://doi.org/10.1039/d5nr02249e
Int J Antimicrob Agents. 2025 Sep 08. pii: S0924-8579(25)00168-2. [Epub ahead of print] 107613

Results of TOR001: an open-label single patient study using targeted bacteriophage therapy for the treatment of a chronic urinary tract infection.

Jonathan D Cook, Payton B Hooey, Keiko C Salazar, Justin R Clark, Umesh Jain, Carlos Fernando, Hanjeong Harvey, Alexander Cervantes, Stephanie Omagari, Udi Blankstein, Andrew M Kropinski, Alan R Davidson, Karen L Maxwell, Lori L Burrows, Austen L Terwilliger, Anthony W Maresso, Greg J German.

  Chronic urinary tract infections are persistent bacterial infections with the potential to drive antibiotic resistance. Like other persistent bacterial infections, intracellular bacterial reservoirs and biofilm formation hinder the clearance of pathogens despite long courses of antibiotic therapy. New strategies for treatment of these persistent infections are needed. Here we describe the results of an open-label individual patient study using bacteriophage therapy to treat a chronic urinary tract infection in an immunocompetent 72-year-old woman without underlying urolithiasis or indwelling devices. We co-administered HP3.1, HP3, and ES19 bacteriophages with demonstrated in vitro activity via bladder instillation, orally, and as a topical formulation. The primary outcome was safety and tolerability of the treatment. Adverse events were monitored through daily symptom logs and laboratory analysis of blood samples obtained throughout the study. We found that the treatment was safe and well tolerated with no serious adverse events reported. No adverse events were deemed related to the study material. The secondary outcomes were clinical and microbiological efficacy as monitored through daily symptom logs and standard urine culture, respectively. Two weeks after initial clinical improvement, her condition relapsed and culture was consistent with previous isolates. Treatment with ertapenem following bacteriophage therapy led to sustained clinical and microbiologic cure. Exploratory analysis through whole genome sequencing of pre- and post-treatment isolates identified mutations in genes associated with adhesion and evasion that may influence virulence and promote clearance. These results inform expanded randomized clinical trials and support the growing literature that bacteriophage therapies are safe and effective.

Keywords:  Escherichia coli; bacteriophage; chronic urinary tract infection; phage therapy

DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107613
Curr Opin Pulm Med. 2025 Sep 04.

New anti-infective approaches to treat airway infections in persons with cystic fibrosis and bronchiectasis.

Justin Massey, Ghady Haidar, Ryan K Shields, Daria Van Tyne.

   PURPOSE OF REVIEW: Cystic fibrosis (CF) and non-CF bronchiectasis can predispose patients to airway infections that are difficult to treat. The purpose of this review is to discuss recently developed anti-infectives which show promise in treating these infections.
RECENT FINDINGS: The microbiology underlying respiratory tract infections in persons with CF (pwCF) and non-CF bronchiectasis is complex. Both traditional and nontraditional anti-infective approaches have recently been discovered and/or are actively being studied for the treatment of airway infections. Traditional antibiotics, including small molecules/compounds/formulations, and nontraditional methods, such as monoclonal antibodies and bacteriophages, have shown promise in their ability to treat airway infections in case studies, case series, and/or clinical trials.
SUMMARY: Several new approaches are currently being developed to better manage airway infections associated with both CF and non-CF bronchiectasis. While many of these new therapies are promising, more studies are needed to assess their safety and efficacy.

Keywords:  airway infections; anti-infectives; antibiotics; bronchiectasis

DOI:  https://doi.org/10.1097/MCP.0000000000001214
Chimia (Aarau). 2025 Sep 10. 79(9): 644-649

Optimizing the Production of Therapeutic Bacteriophages Through Quality by Design: A Case Study on Pseudomonas Aeruginosa.

Carmen Jungo, Samuel Garcia, Jean-François Brunet, Grégory Resch.

  A Failure Modes and Effects Analysis (FMEA) risk assessment was conducted to evaluate and document the criticality of process parameters and material attributes involved in a Pseudomonas aeruginosa phage production process. This assessment was carried out following the principles of Quality by Design (QbD) as outlined by the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use. By systematically identifying and controlling critical factors, this approach contributes to the development of a more robust and reproducible phage production process, ultimately enhancing process efficiency and product quality.

Keywords:  Antimicrobial resistance; Bacteriophages; Phage therapy; Process characterization; Pseudomonas aeruginosa; Quality by Design

DOI:  https://doi.org/10.2533/chimia.2025.644
Proc Natl Acad Sci U S A. 2025 Sep 16. 122(37): e2513377122

Quantifying phage infectivity from characteristics of bacterial population dynamics.

Michael Blazanin, Eli Vasen, Cèlia Vilaró Jolis, William An, Paul E Turner.

  A frequent goal of phage biology is to quantify how well a phage kills a population of host bacteria. Unfortunately, traditional methods to quantify phage success can be time-consuming, limiting the throughput of experiments. Here, we use theory to show how the effects of phages on their hosts can be quantified using bacterial population dynamics measured in a high-throughput microplate reader (automated spectrophotometer). We use mathematical models to simulate bacterial population dynamics where specific phage and bacterial traits are known a priori. We then test common metrics of those dynamics (e.g., growth rate, time and height of peak bacterial density, death rate, extinction time, area under the curve) to determine which best predict: 1) infectivity over the short-term, and 2) phage suppression over the long term. We find that many metrics predict infectivity and are strongly correlated with one another. We also find that metrics can predict phage growth rate, providing an effective way to quantify the combined effects of multiple phage traits. Finally, we show that peak density, time of peak density, and extinction time are the best metrics when comparing across different bacterial hosts or over longer timescales where plasticity or evolution may play a role. In all, we establish a foundation for using bacterial population dynamics to quantify the effects of phages on their bacterial hosts, supporting the design of in vitro empirical experiments using microplate readers.

Keywords:  methods development; simulations; theory

DOI:  https://doi.org/10.1073/pnas.2513377122
J Eur Acad Dermatol Venereol. 2025 Sep 11.

Bacteriophage therapy in dermatology: A systematic review.

Miranda K Branyiczky, Samantha A Mannala, Eric McMullen, Ronald Vender, Mohannad Abu-Hilal, Narachai Julanon, Shireen Dumont, Vincent Piguet.



Keywords:  acne; antibiotic resistance; atopic dermatitis; bacteriophages; hidradenitis suppurativa; wounds

DOI:  https://doi.org/10.1111/jdv.70057
Arch Microbiol. 2025 Sep 11. 207(10): 261

Characterization of the novel Cutibacterium acnes phage KIT08 and its associated pseudolysogenic bacterial isolate.

Phuoc-Dung Nguyen, Koki Nakanishi, Chihiro Hosokawa, Nguyen Song Han, Masao Kitao, Masanao Yoshimoto, Kaeko Kamei.

  Cutibacterium acnes, formerly Propionibacterium acnes, is a Gram-positive bacterium commonly recognized as an important factor in acne vulgaris and infections associated with prosthetic medical devices. With the rise in antibiotic resistance, phage therapy has gained renewed attention as a promising alternative to antibiotics. In addition to a strict lytic cycle, some virulent phages may enter a pseudolysogenic state and exclude superinfections, thereby significantly limiting the applicability of these potential antimicrobial agents. However, the trade-off induced by phage infection of bacterial cells during this state and its molecular mechanism are yet to be confirmed, especially for C. acnes phages. In this study, a novel Cutibacterium acnes phage, KIT08, was isolated and characterized. It demonstrated rapid infectivity and moderately strong bacteriolysis. After infection of C. acnes NBRC 107,605, pseudolysogenic bacteria were collected and examined for physiological tradeoffs. The pseudolysogenic isolate exhibited slower growth and downregulation of the transcriptional levels of biofilm-producing genes, such as lipase 2 and hyaluronate lyase, leading to a decrease in biofilm formation. Additionally, a genomic study of phage KIT08 revealed that open reading frames 23 and 34 encode putative proteins homologous to repressor C and LTP proteins, which may play an important role in the induction of pseudolysogeny and superinfection exclusion in C. acnes.

Keywords:   Cutibacterium acnes ; Cutibacterium phage; Propionibacterium phage; Pseudolysogeny; Superinfection exclusion

DOI:  https://doi.org/10.1007/s00203-025-04451-8
Polymers (Basel). 2025 Aug 26. pii: 2303. [Epub ahead of print]17(17):

Progressive Hydrogel Applications in Diabetic Foot Ulcer Management: Phase-Dependent Healing Strategies.

Priyanka Mallanagoudra, Sai Samanvitha M Ramakrishna, Sowmya Jaiswal, Dhruthi Keshava Prasanna, Rithika Seetharaman, Arunkumar Palaniappan, Sudarshan Kini.

  Diabetes is emerging as a significant health and societal concern globally, impacting both young and old populations. In individuals with diabetic foot ulcers (DFUs), the wound healing process is hindered due to abnormal glucose metabolism and chronic inflammation. Minor injuries, blisters, or pressure sores can develop into chronic ulcers, which, if left untreated, may lead to serious infections, tissue necrosis, and eventual amputation. Current management techniques include debridement, wound dressing, oxygen therapy, antibiotic therapy, topical application of antibiotics, and surgical skin grafting, which are used to manage diabetic wounds and foot ulcers. This review focuses on a hydrogel-based strategy for phase-wise targeting of DFUs, addressing sequential stages of diabetic wound healing: hemostasis, infection, inflammation, and proliferative/remodeling phases. Hydrogels have emerged as a promising wound care solution due to their unique properties in providing a suitable wound-healing microenvironment. We explore natural polymers, including hyaluronic acid, chitosan, cellulose derivatives, and synthetic polymers such as poly (ethylene glycol), poly (acrylic acid), poly (2-hydroxyethyl methacrylate, and poly (acrylamide), emphasizing their role in hydrogel fabrication to manage DFU through phase-dependent strategies. Recent innovations, including self-healing hydrogels, stimuli-responsive hydrogels, nanocomposite hydrogels, bioactive hydrogels, and 3D-printed hydrogels, demonstrate enhanced therapeutic potential, improving patient outcomes. This review further discusses the applicability of various hydrogels to each phase of wound healing in DFU treatment, highlighting their potential to advance diabetic wound care through targeted, phase-specific interventions.

Keywords:  diabetic foot ulcer; hydrogel; inflammation; microenvironment; wound healing

DOI:  https://doi.org/10.3390/polym17172303
Virology. 2025 Sep 06. pii: S0042-6822(25)00299-5. [Epub ahead of print]612 110685

Characterization of phage vB_EfS_C1 and investigation of antibacterial and antibiofilm properties against vancomycin-susceptible and vancomycin-resistant Enterococcus faecium.

Mohamed El-Telbany, Keigo Yamamura, Norihiro Saito, Yoshimitsu Masuda, Takahisa Miyamoto, Ken-Ichi Honjoh.

  E. faecium is listed among the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter), which are responsible for a significant proportion of global deaths. Vancomycin-resistant E. faecium (VREfm) is the leading species responsible for human infections, and the limited therapeutic options make VREfm a public health problem. This study aimed to isolate and characterize a novel phage against E. faecium and evaluate its activity against vancomycin-sensitive E. faecium (VSEfm) and VREfm. We isolated a phage, named vB_EfS_C1, from compost. The host range analysis showed that it produced plaques on 5 out of 18 enterococci strains and did not produce plaques on other species. Phage vB_EfS_C1 was infective at different temperatures (40-70 °C), and the titer was stable at different pH levels (6-9). The phage vB_EfS_C1 is 86,777 bp in length, grouping it with phages with large genomes infecting enterococci (>80 kbp). The killing curve revealed that phage vB_EfS_C1 had antibacterial activity with different MOIs (0.001-1) against the E. faecium host strain. The biofilm biomass of E. faecium FHC29 was reduced by 85 % after 6 and 24 h, and the biofilm biomass of E. faecium No. 982 (VREfm) by 50 % after 6 h and 25 % after 24 h with an MOI of 0.1. The viable counts of E. faecium FHC29 and VREfm in biofilms were decreased by 3 log and 1.83 log with an MOI of 1, respectively. In conclusion, phage vB_EfS_C1 is a lytic enterococcal phage displaying antibiofilm activity against VSEfm and VREfm.

Keywords:  And vancomycin resistance; Bacteriophage; Biofilm; Enterococcus faecium

DOI:  https://doi.org/10.1016/j.virol.2025.110685
Animals (Basel). 2025 Aug 27. pii: 2525. [Epub ahead of print]15(17):

Environmental Application of a Bacteriophage Cocktail Reduces Antibiotic-Resistant Escherichia coli in Poultry Litter Without Disrupting Gut Microbiota.

Marta Kuźmińska-Bajor, Maciej Kuczkowski, Damian Konkol, Mariusz Korczyński, Magdalena Rakicka-Pustułka, Sylwia Kozioł, Ludwika Tomaszewska-Hetman, Anita Rywińska.

  The increasing demand for poultry meat calls for sustainable production methods that address animal welfare and combat antimicrobial resistance (AMR). Commensal Escherichia coli serve as reservoirs of resistance genes that may transfer to pathogens, facilitating AMR spread in agriculture. This study evaluated the efficacy of a bacteriophage cocktail, UPWr_E, applied as a litter spray to reduce total and antibiotic-resistant E. coli in broiler chicken rearing. The cocktail, containing four lytically active phages, was administered for four weeks. Microbiological analyses of litter, feces, and cecal contents showed a significant reduction in total E. coli by 3.2 log10 CFU/g in litter and a decrease in resistant strains to gentamicin, enrofloxacin, tetracycline, and sulfamethoxazole-trimethoprim, compared to controls. No significant changes occurred in E. coli loads in feces or cecal contents, indicating limited impact on the number of commensal E. coli in cecal contents. Phages remained detectable and stable in litter and feces throughout the study. These findings demonstrate the potential of phage therapy as a targeted, environmentally friendly approach to control AMR reservoirs in poultry farming. Incorporating phage-based treatments into AMR management strategies could improve food safety and promote sustainable animal production.

Keywords:  AMR; E. coli; bacteriophages; broiler chickens; litter; phage treatment

DOI:  https://doi.org/10.3390/ani15172525
Am J Physiol Lung Cell Mol Physiol. 2025 Sep 08.

Mesenchymal Stromal Cell Extracellular Vesicles Reduce Pseudomonas Biofilm Formation, and let-7b-5p Loading Confers Additional Anti-Inflammatory Effects.

Sharanya Sarkar, Roxanna Barnaby, Amanda B Nymon, Lily A Charpentier, Lily Taub, Matthew J Wargo, Daniel J Weiss, Tracey L Bonfield, Bruce A Stanton.

  Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the CFTR gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, Pseudomonas aeruginosa is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies. Our group engineered mesenchymal stromal cell derived extracellular vesicles (MSC EVs) to carry the microRNA let-7b-5p as a dual anti-infective and anti-inflammatory treatment. MSC EVs are low-immunogenicity platforms with innate antimicrobial and immunomodulatory properties, while let-7b-5p reduces inflammation. This study demonstrates that MSC EVs effectively blocked the formation of antibiotic-resistant P. aeruginosa biofilms on primary Human Bronchial Epithelial Cells (pHBECs), and let-7b-5p loading into MSC EVs conferred additional anti-inflammatory effects by reducing P. aeruginosa-induced IL-8 secretion by pHBECs. This approach holds promise for improving outcomes for people with CF, and future work will focus on optimizing delivery strategies and expanding the clinical applicability of MSC EVs to target other CF-associated pathogens.

Keywords:  Cystic Fibrosis; Human Bronchial Epithelial Cells; Inflammation; Mesenchymal Stromal Cell Extracellular Vesicles; Pseudomonas aeruginosa biofilms

DOI:  https://doi.org/10.1152/ajplung.00187.2025
Int J Biol Macromol. 2025 Sep 05. pii: S0141-8130(25)08032-8. [Epub ahead of print] 147475

A review of biomimetic hydrogel wound dressings: Design inspiration, construction strategies, multifunctionality and applications.

Linhan Feng, Yujiao Shi, Ziyun Wang, Chunxiao Wang, Yinuo Fan, Ning Wang, Shuying Liu, Junchen Wei, Xinyu Zhang, Panpan Pan, Jingdi Chen.

  The treatment of chronic hard-to-heal wounds has become a major medical and public health problem worldwide. The search for novel and efficient wound healing dressings is crucial because of the complex mechanisms of wound genesis and of the inability to spontaneously repair. Many inherent properties of organisms in nature and their intrinsic molecular mechanisms have inspired researchers to design biomimetic hydrogel wound dressings to treat chronic hard-to-heal wounds. In this review, the design inspiration, intrinsic mechanisms, and construction strategies of biomimetic polymer hydrogels are discussed in depth from three aspects: compositional biomimicry, structural biomimicry, and behavioral biomimicry. The multifunctionality of biomimetic polymer hydrogels and their application progress in the treatment of chronic hard-to-heal wounds are elaborated. Challenges to the smart and functional integration of biomimetic polymer hydrogels are summarized, and their future clinical applications are envisioned. This review provides new ideas and directions for the design and development of novel biomimetic polymer hydrogels for repair engineering in skin tissues, articular cartilage, and other places.

Keywords:  Biomimetic; Construction strategy; Design inspiration; Hydrogel; Wound dressing

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147475
J Clin Med. 2025 Aug 25. pii: 5987. [Epub ahead of print]14(17):

Infectious Keratitis Management: 10-Year Update.

Neel D Pasricha, Pablo Larco, Darlene Miller, Diego S Altamirano, Jennifer R Rose-Nussbaumer, Eduardo C Alfonso, Guillermo Amescua.

  Infectious keratitis (IK), including bacterial, fungal, parasitic, and viral etiologies, continues to represent a significant cause of ocular morbidity in the United States and around the world. Corneal scraping for smears and cultures remains the gold standard in diagnosing IK; however, molecular diagnoses, including metagenomic deep sequencing (MDS), are promising emerging diagnostic tools. Despite recent interest in procedural treatment such as riboflavin photoactivated chromophore corneal collagen cross-linking (PACK-CXL) and Rose Bengal photodynamic antimicrobial therapy (RB-PDAT), medical treatment advances have remained stagnant. Methods: This review highlights IK pathogens obtained from corneal cultures at Bascom Palmer Eye Institute (BPEI) from 2011 to 2021 and provides the current BPEI algorithms for initial management of IK or as a referred clinically worsening patient. The roles of corticosteroid therapy, PACK-CXL, and RB-PDAT for IK are also summarized. Results: A total of 9326 corneal cultures were performed at BPEI between 2011 and 2021, and only 3609 (38.7%) had a positive organism identified, of which bacteria were the most common (83.4%). Fortified vancomycin and tobramycin are recommended as first-line medical therapy for IK patients based on culture sensitivity data for the top Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. PACK-CXL and RB-PDAT may benefit IK patients with corneal melting and fungal IK, respectively. Conclusions: Drug holidays, minimizing contamination, and optimizing sample order are crucial to maximizing corneal culture positivity. PACK-CXL and RB-PDAT are promising procedural advancements for IK therapy.

Keywords:  antimicrobial therapy; corneal ulcer; infectious keratitis

DOI:  https://doi.org/10.3390/jcm14175987
Nat Rev Mol Cell Biol. 2025 Sep 09.

Learning about break-induced replication from bacteriophages.

James E Haber.

DOI: https://doi.org/10.1038/s41580-025-00898-1
J Pharmacol Exp Ther. 2025 Jul 15. pii: S0022-3565(25)39872-1. [Epub ahead of print]392(9): 103659

Pharmacological insights into gut microbiota modulation in systemic lupus erythematosus: Mechanisms, treatment strategies, and clinical implications.

Kantrol Kumar Sahu, Krishna Yadav, Madhulika Pradhan, Mukesh Sharma, Akhilesh Dubey, Sucheta, J John Kirubakaran.

  Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by widespread inflammation and immune system dysregulation. Recent research suggests that the gut microbiota may play a role in the development of SLE by modulating immune system responses, affecting cytokine production, and altering the activity of T and B cells lymphocytes. As a result, there is a growing interest in microbiota-targeted therapies, including probiotics, dietary changes, and fecal microbiota transplantation. These methods may help restore the balance of microbes and reduce disease activity, but there are still a number of problems to solve. For example, microbiota composition varies greatly from person to person, and it is not clear how dysbiosis causes disease onset. There are also safety concerns about fecal microbiota transplantation. Experimental and clinical studies have started to shed light on the complicated ways in which microbial communities and immune function affect each other in SLE. These studies provide useful information, but their results are often inconsistent. As research continues, integrative methods like metagenomics and metabolomics may help find microbial signatures linked to disease, helping create more accurate and personalized treatments. The gut microbiome is a promising yet still developing area of research that could help us learn more about autoimmune diseases and their treatment, such as SLE. SIGNIFICANCE STATEMENT: Grasping the complex interplay between gut microbiota and systemic lupus erythematosus (SLE) has provided an avenue for therapeutic intervention. This study emphasizes the importance of gut dysbiosis in immune dysregulation, with connections between microbial translocation, molecular mimicry, and inflammatory pathways as contributing factors to the progression of SLE. This work sets the stage for novel and targeted approaches to treating SLE and improving patient outcomes by investigating microbiota-centric treatment options, such as probiotics, dietary interventions, and fecal microbiota transplantation.

Keywords:  Gut-immune axis; Immune dysregulation; Leaky gut; Microbial translocation; Molecular mimicry; Systemic lupus erythematosus

DOI:  https://doi.org/10.1016/j.jpet.2025.103659
Open Life Sci. 2025 ;20(1): 20251166

Wound healing and signaling pathways.

Zhe Liu, Yudong Fang.

  Wound healing is a precisely regulated dynamic process in which signaling pathways play a central role. This article provides a comprehensive review of the signaling pathways involved in wound healing, emphasizing their roles in inflammation, vascular regeneration, cell proliferation, and extracellular matrix remodeling. We further discuss the crosstalk between these pathways and their contributions to wound healing dysregulation. Finally, we explore emerging therapeutic strategies targeting these pathways, including small-molecule inhibitors, gene therapy, and biologics, summarizing their preclinical and clinical efficacy. By elucidating the molecular mechanisms underlying wound healing and potential interventions, this review aims to provide valuable insights for future research and translational applications in wound healing.

Keywords:  crosstalk; signaling pathway; therapeutic strategies; wound healing

DOI:  https://doi.org/10.1515/biol-2025-1166
Anim Reprod. 2025 ;22(3): e20250030

Fundamentals of microbiome-based therapies for reproductive tract inflammatory diseases in domestic animals.

Uxía Yáñez Ramil, Sylwia Jezierska, Milena Krupa, Osvaldo Bogado Pascottini.

  Reproductive tract inflammatory diseases (RTID) present significant health challenges in domestic animals, impacting welfare, fertility, and productivity. Traditionally, antibiotics have been the primary treatment for these conditions, however, the rise of antimicrobial resistance calls for alternative approaches. The microbiome of the female reproductive tract plays a vital role in maintaining reproductive health, and emerging evidence suggests that microbiome-based therapies, such as 'natural' or 'synthetic' microbiome transplantation, may offer sustainable solutions for RTID management. This review explores the composition and dynamics of the reproductive microbiome in both healthy and diseased states in cows, mares, sows, dogs, and cats. It also examines current treatments and the potential for microbiome-based interventions to replace or complement antibiotic therapies. Although research on microbiome-based therapies for preventing or treating RTID in domestic animals is virtually non-existent, vaginal and uterine microbiomes transplantation in mice and women show promise but require further investigation to evaluate their efficacy and safety across species with varying reproductive physiologies. Additionally, synthetic microbiome therapies present a controlled and reproducible alternative, though they face challenges in design, engraftment, and regulatory approval. The transition from antibiotic dependence to microbiome-based solutions marks a paradigm shift in veterinary medicine, but successful implementation demands a deeper understanding of host-microbiome interactions, rigorous safety protocols, and species-specific research.

Keywords:  antibiotic resistance; microbiome transfer; microbiota; synthetic microbiome; therapeutics; uterine disease

DOI:  https://doi.org/10.1590/1984-3143-AR2025-0030