bims-fagtap 2025-08-24 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–08–24
24 papers selected by
Luca Bolliger, lxBio

Temperate phages increase antibiotic effectiveness in a Caenorhabditis elegans infection model.
Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa.
Cystic fibrosis and inflammatory bowel disease: parallels in gut physiology and microbiota.
Computational function prediction of bacteria and phage proteins.
The broad-spectrum kayvirus phage disrupts biofilms formed by methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius.
Lytic bacteriophages targeting multidrug-resistant Pseudomonas aeruginosa in Moschus berezovskii: isolation, characterization, and therapeutic efficacy against bacteremia.
Plasma-activated water accelerates wound healing and reduces Staphylococcus aureus infection in vivo.
Natural products influence bacteriophage infectivity.
Role of methicillin-resistant Staphylococcus aureus in cutaneous infections: Current treatments and therapeutic approaches for future advancement.
Wound Infection After Keloid Excision and Adjuvant Radiotherapy: Two Case Reports and Literature Review.
Probiotics in inflammatory bowel diseases: emphasis on mechanisms and clinical application.
Antibiotics and phages drive region-specific diversity of OmpK36 in Klebsiella pneumoniae.
Knowledge, Attitudes and Practices of Healthcare Providers on Antibiotics Use and Resistance in Hospital Settings in Kinshasa, Democratic Republic of Congo.
Real‑world safety and efficacy of biological agents in inflammatory bowel disease: a one-year post-marketing pharmacovigilance observational study in the Calabria region.
Biofilm-associated Escherichia coli infections: pathogenesis, clinical implications, and treatment strategies.
Synergistic effects of commensals and phage predation in suppressing colonization by pathogenic Vibrio parahaemolyticus.
Nitrogen availability shapes evolution of phage resistance in cyanobacteria.
Lytic bacteriophage disrupts biofilm and inhibits growth of pan-drug-resistant Listeria monocytogenes in dairy products.
Human augmentation to deliver an enhanced and resilient people capability for Defence.
Delivered baicalein immunomodulatory hydrogel with dual properties of pH-responsive and anti-infection orchestrates pro-regenerative response of macrophages for enhanced hypertrophic scars therapy.
Controlling nanocage assembly, towards developing a one-health "plug & play" platform for targeted therapy.
Research trends and topics on sepsis immunosuppression: a bibliometric and visual analysis of global research from 2004 to 2024.
Unmasking Pathogen Traits for Chronic Colonization in Neurogenic Bladder Patients.
A prevalent huge phage clade in human and animal gut microbiomes.

mBio. 2025 Aug 18. e0162125

Temperate phages increase antibiotic effectiveness in a Caenorhabditis elegans infection model.

Rabia Fatima, Gayatri Nair, Jordan Mayol, Lesley T MacNeil, Alexander P Hynes.

  The bactericidal nature of obligately lytic bacterial viruses (phages) is of increasing interest for the treatment of drug-resistant bacterial infections, often alongside antibiotics. By contrast, temperate phages are largely ignored due to their ability to lie dormant within the bacterial host. However, these phages often undergo a lytic cycle. Furthermore, in their dormant state, they switch to lytic replication in response to triggers, such as antibiotics, that stress the bacterial host. Recent reports of antibiotics synergizing with temperate phages in vitro, termed "temperate phage-antibiotic synergy" (tPAS), present a potentially scalable opportunity to make use of these abundant entities in therapy. Here, we employ Caenorhabditis elegans as a model to test the efficacy of temperate phages. In vivo, temperate phage Hali alone results in 60% dormancy in the bacterial survivors. However, the antibiotic ciprofloxacin can abolish dormancy of the phage-even in a ciprofloxacin-resistant Pseudomonas aeruginosa clinical strain. The phage Hali-ciprofloxacin pairing increased the lifespan of P. aeruginosa-infected worms to that of the uninfected control, at doses where neither the phage nor the antibiotic had any effect alone. Complete rescue was also observed in worms infected with a phage-carrying strain treated with the otherwise ineffective antibiotic, supporting that the phage-even in its dormant form-can greatly enhance antibiotic effectiveness. This illustrates potential "accidental" phage therapy when antibiotics are prescribed. As the first in vivo demonstration of tPAS, our work establishes C. elegans as a model for studying it, greatly expanding the therapeutic potential of temperate phages.
IMPORTANCE: Bacterial viruses (phages), which can go dormant in their host, are not considered suitable for phage therapy. Building on prior work showing antibiotics synergize with these phages by preventing dormancy, we test the ability of temperate phages-in combination with antibiotics-in an animal model of infection. Not only were the combinations extremely effective at doses that would do nothing alone, even when the bacterium was resistant to the antibiotics-but we also found that whether the dormant phage pre-existed (as it does in about 75% of bacteria) or not determined the success of antibiotic treatments, suggesting many antibiotic treatments are already a form of "accidental" phage therapy.

Keywords:  C. elegans; bacteriophage therapy; induction; lysogeny; phage antibiotic synergy; temperate phages

DOI:  https://doi.org/10.1128/mbio.01621-25
Sci Rep. 2025 Aug 19. 15(1): 30439

Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa.

Abishek Mani, Aarcha Shanmugha Mary, Nashath Kalangadan, Srivignesh Sundaresan, Somnath Ghosh, John Prakash, Siva Sundara Kumar Durairajan, Kaushik Rajaram.

  Humanity could descend into a pre-antibiotic world as a result of antimicrobial resistance (AMR). Phage defenses are considered "vintage heroes" in the battle against multidrug-resistant (MDR) bacteria. However, phage resistance continues to evolve, necessitating alternative strategies. A potential solution is combining phages with antimicrobials like silver nanoparticles (AgNPs) to enhance the phage therapy. This study focuses on a combination therapy using Bauhinia variegata L.-mediated AgNPs and Pseudomonas phage M12PA to target multidrug-resistant (MDR) Pseudomonas aeruginosa. The antibacterial properties of this combination were evaluated through comprehensive characterizations and assays. As a proof of concept, the AgNP-phage combination delayed phage resistance by 6-12 h, reduced mutation, and enhanced antibacterial efficiency. Anti-biofilm activity improved by ~ 40% compared to AgNPs alone at sub-inhibitory concentrations. AgNPs and phages have demonstrated excellent compatibility, and the phage titer did not drop noticeably over 30 days. Biocompatibility assessments, including cell viability and hemolysis assays, highlighted the safety of biosynthesized AgNPs. Wound healing efficacy was also demonstrated in mouse fibroblast cells and an in ovo angiogenesis model. This study underscores the efficiency of phage-AgNPs synergy to be a potential therapeutic approach for MDR bacterial wound infection, showing effective anti-biofilm activity, delayed phage resistance, and minimal toxicity.

Keywords:   In ovo angiogenesis; In ovo infection model; Anti-biofilm activity; Biosynthesized AgNPs; Delayed phage resistance; Phage therapy

DOI:  https://doi.org/10.1038/s41598-025-00449-w
J Bacteriol. 2025 Aug 18. e0016725

Cystic fibrosis and inflammatory bowel disease: parallels in gut physiology and microbiota.

Kaitlyn E Barrack, George A O'Toole.

  Cystic fibrosis (CF) and inflammatory bowel disease (IBD) represent distinct pathologies with unique genetic underpinnings; yet, they share remarkable similarities in gut microbiota dysbiosis and intestinal physiology. This review comprehensively examines the parallels and differences between these conditions, focusing on microbial signatures, inflammatory markers, and physiological features. Both diseases exhibit increased levels of Proteobacteria, decreased anaerobic short-chain fatty acid producers, and altered intestinal metabolic profiles. Common physiological characteristics include intestinal inflammation with elevated inflammatory markers (calprotectin, S100A12, lactoferrin), lower intestinal pH, and similar bile acid dysregulation patterns. However, key differences emerge in mucus characteristics, disease onset timing, and current treatment approaches. The gut microbiota plays a crucial role in both conditions, with shared signatures of dysbiosis suggesting similar intestinal environmental shifts and potential common therapeutic targets. Recent advances in CFTR modulator therapy have shown promising effects on the CF gut microbiome, while IBD treatments demonstrate variable efficacy. Understanding these similarities and differences is crucial for developing targeted therapies that could benefit both populations. This review highlights the complex interplay between host genetics, environmental factors, and the gut microbiota, emphasizing the need for further research to disentangle these relationships. We also discuss how the information provided here can be used to build and validate in vitro models to study the dysbiotic microbial communities and their causes in these diseases, to develop more effective treatments.

Keywords:  cystic fibrosis; dysbiosis; inflammatory bowel disease; microbiome

DOI:  https://doi.org/10.1128/jb.00167-25
Microbiol Mol Biol Rev. 2025 Aug 18. e0002225

Computational function prediction of bacteria and phage proteins.

Susanna R Grigson, George Bouras, Bas E Dutilh, Robert D Olson, Robert A Edwards.

  SUMMARYUnderstanding protein functions is crucial for interpreting microbial life; however, reliable function annotation remains a major challenge in computational biology. Despite significant advances in bioinformatics methods, ~30% of all bacterial and ~65% of all bacteriophage (phage) protein sequences cannot be confidently annotated. In this review, we examine state-of-the-art bioinformatics tools and methodologies for annotating bacterial and phage proteins, particularly those of unknown or poorly characterized function. We describe the process of identifying protein-coding regions and the systems to classify protein functionalities. Additionally, we explore a range of protein annotation methods, from traditional homology-based methods to cutting-edge machine learning models. In doing so, we provide a toolbox for confidently annotating previously unknown bacterial and phage proteins, advancing the discovery of novel functions and our understanding of microbial systems.

Keywords:  bioinformatics; function prediction; machine learning; microbial proteins

DOI:  https://doi.org/10.1128/mmbr.00022-25
Virology. 2025 Aug 14. pii: S0042-6822(25)00270-3. [Epub ahead of print]611 110657

The broad-spectrum kayvirus phage disrupts biofilms formed by methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius.

Sukanya Apiratwarrasakul, Pathomporn Sresuwadjarey, Nathita Phumthanakorn, Patoo Withatanung, Metawee Thongdee, Varintip Lerdsittikul.

  The escalating global challenge of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP) demands innovative therapeutic approaches. This study comprehensively characterized Staphylococcus phage vB_SauM_VL14 (VL14), a virulent bacteriophage from the Herelleviridae family (Twortvirinae subfamily, Kayvirus genus) with a 141,584-bp linear double-stranded DNA genome. Genomic analysis confirmed that phage VL14 is strictly lytic, containing 224 ORFs and four tRNAs, without lysogenic, virulence, or antimicrobial resistance genes. Phage VL14 demonstrated a 30-min latent period with a burst size of 110 PFU. Host range analysis revealed broad activity, lysing 100 % of S. aureus and 60 % of S. pseudintermedius isolates, including methicillin-resistant strains. The phage achieved significant bacterial reductions and exhibited remarkable biofilm-disrupting capabilities, substantially reducing the biofilm mass and viable cell counts. These findings establish phage VL14 as a broad-spectrum lytic phage with potent bactericidal and biofilm-disrupting activity, supporting its potential as a therapeutic agent against multidrug-resistant Staphylococcus infections and warranting further evaluation in in vivo and clinical settings.

Keywords:  Antibiotic resistance; Bacteriophage; Biofilm; MRSA; MRSP; Staphylococcus aureus; Staphylococcus pseudintermedius

DOI:  https://doi.org/10.1016/j.virol.2025.110657
Virol J. 2025 Aug 19. 22(1): 285

Lytic bacteriophages targeting multidrug-resistant Pseudomonas aeruginosa in Moschus berezovskii: isolation, characterization, and therapeutic efficacy against bacteremia.

Qingxia Hu, Yanjie Zhang, Ni Lv, Yahao Kang, Saba Nasir, Ruiqing Wang, Jiahao Qu, Jiadeng Jiang, Xiao Li, Xinglong Wang.

  Pseudomonas aeruginosa (P. aeruginosa) is an important zoonotic pathogen. It is also the primary causative agent of systemic infections in the endangered Moschus berezovskii. The emergence of multidrug-resistant strains of P. aeruginosa has made these infections increasingly difficult to control, and bacteriophages are considered important alternatives or adjuncts to antibiotic therapy. This study isolated P. aeruginosa strains that induce suppurative infections in Moschus berezovskii from a farm in Shaanxi Province, China. The bacteriophages vB_PaeP_FMD5 (FMD5) and vB_PaeM_H24-1 (H24-1) were isolated using these bacteria as hosts. The safety and practicality of the two phages were analyzed through methods such as biological characteristic assessment, whole genome sequencing analysis, and animal experiments. FMD5 is classified within the Podoviridae family, whereas H24-1 belongs to Myxoviridae. Biological characterization revealed that both FMD5 and H24-1 exhibit tolerance to temperature, pH, chloroform, and Ultraviolet(UV) exposure. The optimal multiplicity of infection (OMOI) for FMD5 and H24-1 were 0.01 and 0.1, respectively, and the burst sizes from the one-step growth curve were 200 PFU/cell and 150 PFU/cell, respectively. In vitro inhibitory assays demonstrated that FMD5, H24-1, and their cocktail exerted a favorable inhibitory effect for up to 11 hours. Whole genome sequencing confirmed that both phages possess double-stranded DNA genomes, with FMD5 having a length of 72,254 bp and a G+C content of 55.16%, containing 91 ORFs(Open Reading Frame), whereas H24-1 has a genome length of 66,281 bp, a G+C content of 56.26%, and encompasses 94 ORFs. No drug-resistance genes, virulence factors, or lysogenic genes were identified in either phage. Phylogenetic analysis of conserved genes revealed that FMD5 is closely related to the previously published Pseudomonas phage LP14 (LP14), while H24-1 is closely related to the previously published Pseudomonas phage vB_PaeM_LS1(LS1), but both are newly discovered bacteriophages. In a mouse model of bacteremia treated with bacteriophages, both individual phages and the cocktail exhibited favorable therapeutic effects. The two novel bacteriophages isolated in this study exhibit efficient and stable characteristics. They demonstrate sound therapeutic effects against bacteremia in mice caused by multidrug-resistant P. aeruginosa, suggesting their great potential as alternatives or adjuncts to antibiotic therapy for treating infection.

Keywords:   Moschus berezovskii ; Pseudomonas aeruginosa ; Complete genome; Mouse bacteremia model; Phage vB_PaeM_H24 - 1; Phage vB_PaeP_FMD5

DOI:  https://doi.org/10.1186/s12985-025-02715-9
Biofilm. 2025 Dec;10 100308

Plasma-activated water accelerates wound healing and reduces Staphylococcus aureus infection in vivo.

Adrian I Abdo, Hang T Nguyen, Laurine D Kaul, Thomas Schmitt-John, Zlatko Kopecki, Abiodun D Ogunniyi, Katharina Richter.

  Chronic wound infections are notoriously difficult to treat due to bacterial biofilms - protective communities of microbes that can resist antibiotics and host defenses. With rising antimicrobial resistance, there is an urgent need for non-antibiotic therapies that can effectively disrupt biofilms and promote wound healing. Plasma-activated water (PAW), produced by bubbling cold plasma into water, creates an antimicrobial solution rich in reactive oxygen and nitrogen species. In this study, we investigated the efficacy of PAW as a topical wound cleanser. In vitro, we demonstrated that PAW effectively eradicated biofilm-forming bacteria, including Staphylococcus spp., Acinetobacter baumannii and Escherichia coli, achieving a reduction of 2.99-4.41 log10(colony forming units [CFU]/mL). In vivo, PAW significantly improved Galleria mellonella larvae survival from infection with methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis. Moreover, we treated scald burn wounds infected with bioluminescent MRSA biofilm in BALB/c mice with twice-daily topical PAW application. Compared to vehicle, PAW significantly reduced bacterial load from day 4-7 (0.44-0.49 log10[photons/s] reduction, p ≤ 0.0337), with endpoint analysis confirming a 1.33 log10[CFU/g] reduction (p = 0.0032). Histological assessment showed significantly improved wound re-epithelialisation in PAW-treated mice (63.2 %) compared to vehicle (49.2 %, p = 0.0093). These results demonstrate that PAW is a safe, effective antimicrobial wound cleanser with biofilm-disrupting and tissue-healing properties. Based on these findings, a clinical phase I trial is planned to evaluate PAW as an adjuvant to standard wound care in the treatment of diabetic foot wounds.

Keywords:  Antibiotic alternative therapies; Biofilm; Cold plasma; Plasma-activated water; Staphylococcus aureus; Wound healing; Wound infection

DOI:  https://doi.org/10.1016/j.bioflm.2025.100308
Nat Prod Rep. 2025 Aug 18.

Natural products influence bacteriophage infectivity.

Zhiyu Zang, Joseph P Gerdt.

Covering: 1942-2025Bacteriophages (phages) are obligate viruses that infect bacteria. The antibacterial effects of both phages and natural products shape microbial ecosystems and have yielded competing antibiotic strategies. Phages have also intersected many times with natural products research throughout the past century. To discover antiviral leads, natural products were screened for anti-phage activity. To discover new anti-cancer drugs, natural products were screened for the ability to trigger lysis by the λ prophage-indicating DNA damage. Now, the antibiotic resistance crisis motivates the study of natural products that can synergize with phages to improve antibacterial therapies. Beyond applications, these parallel natural "chemical" and "biological" antibacterial factors combine to shape microbial communities across our planet. Here, we provide a comprehensive overview of natural products that modulate phage activities. We discuss their mechanisms of action, and we present opportunities for future research.

DOI: https://doi.org/10.1039/d5np00014a
Int J Pharm. 2025 Aug 14. pii: S0378-5173(25)00867-1. [Epub ahead of print] 126030

Role of methicillin-resistant Staphylococcus aureus in cutaneous infections: Current treatments and therapeutic approaches for future advancement.

Adviti Thomas, Nour Almsallaty, Tamim Chalati, Joshua Boateng, Asma Buanz, Ana Maria Totea.

  Antibiotics are often prescribed as a first-line treatment for bacterial skin infections, particularly in severe and persistent cases. However, the ability of the pathogen to develop antibiotic resistance complicates the treatment of these diseases. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the primary microorganisms implicated in skin and soft tissue infections, such as Cellulitis, Impetigo, and infections secondary to Atopic Dermatitis (AD) and has exerted significant pressure on the healthcare industry due to its resistance to conventional antibiotics, including beta-lactams. Skin infections caused by this Gram-positive superbug can occur in individuals even without commonly known risk factors, and thus, there is an urgent necessity to develop novel therapeutic strategies that function beyond traditional antibiotics. Research on alternative treatments, including plant-derived compounds, antimicrobial peptides (AMPs), bacteriophages, and antibiotic sensitisers, is garnering attention as a promising and innovative approach. Numerous studies have demonstrated the capacity of these compounds to inhibit pathogenic bacteria like MRSA. These novel compounds target bacteria through diverse mechanisms, inhibit biofilm formation, and mitigate resistance development. Topically administered treatments are preferred for MRSA-related skin infections; however, cytotoxicity, skin penetration, and in vivo efficacy testing remain a significant challenge. This review provides an overview of the mechanisms contributing to the pathogenesis of MRSA skin infections and investigates alternative therapeutic options to the common antibiotics. An indirect antibacterial approach that uses conventional antibiotics combined with non-antibiotics aims to enhance therapeutic efficacy and overcome resistance by disrupting bacterial defences and biofilm formation, thereby reducing the required antibiotic dosage and minimising adverse effects.

Keywords:  Antibiotic resistance; Antibiotic sensitizers; Antimicrobial peptide; Bacteriophages; Essential oils; Methicillin-resistant Staphylococcus aureus; Non-steroidal anti-inflammatory drugs; Plant compounds; Soft-skin tissue infection; Synergy

DOI:  https://doi.org/10.1016/j.ijpharm.2025.126030
Clin Cosmet Investig Dermatol. 2025 ;18 1943-1951

Wound Infection After Keloid Excision and Adjuvant Radiotherapy: Two Case Reports and Literature Review.

Qinyuan Zhao, Yuyan Wang, Jinsheng Li, Chuanbo Liu.

   Introduction: The combination of surgical excision and adjuvant radiotherapy is widely accepted as one of the most effective treatments for keloids. Although wound infection following radiotherapy has been reported in several studies, no study has investigated how such infections are managed or whether they ultimately lead to keloid recurrence.
Case Reports: Two patients, one male with an anterior chest keloid and one female with a mons pubis keloid, underwent surgical excision followed by adjuvant radiotherapy (20 Gy in four fractions) at our institution. Both patients developed wound infections following combined therapy, both of which were successfully treated using a comprehensive protocol. This protocol involved wound drainage and debridement, antibiotic administration, and moist wound healing. Complete healing was achieved in both cases, with no recurrence observed during the 18-month follow-up period.
Discussion: The possible causes of radiation-induced infection were analyzed, including radiation itself, atopic dermatitis and specific surgical areas (such as the mons pubis region). Our study successfully addressed wound infection by adopting an effective treatment protocol involving wound drainage and debridement, antibiotic administration, and moist wound healing. Although favorable results were obtained in the two keloid cases, optimizing radiotherapy in terms of radiation mode, dosage, fraction and timing is still necessary to reduce the incidence of radiation-induced wound infections.
Conclusion: Neither of the two patients experienced keloid recurrence when treated with an effective therapy for wound infection. This result demonstrates that a favorable outcome can be achieved with the appropriate and timely treatment protocol, even if an infection occurs after radiotherapy. Further clinical studies and basic research are needed to investigate the underlying mechanisms of the favorable outcome following radiation-induced infections.

Keywords:  excision; keloid; radiotherapy; wound infection

DOI:  https://doi.org/10.2147/CCID.S545846
Front Med (Lausanne). 2025 ;12 1620079

Probiotics in inflammatory bowel diseases: emphasis on mechanisms and clinical application.

Junxiang Zhang, Xiaoman Zhang, Xiaoxin Cheng, Shijin Wang, Yangxuan Lv, Xu Zheng, Guangzhen Wu.

  Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic intestinal inflammation including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, probiotics have attracted more and more attention as a potential adjuvant therapy. Probiotics can improve the symptoms and quality of life of IBD patients mainly by regulating intestinal microflora, regulating immune response, enhancing intestinal barrier function and exerting anti-inflammatory effect. However, although a large number of studies have explored the role of probiotics, there are still individual differences and uncertainties in clinical application. This paper reviews the mechanism, clinical effect and future prospect of probiotics in the treatment of IBD, and analyzes the existing clinical research and experimental data to provide reference for further research. Finally, this paper looks forward to the research direction of probiotics in the treatment of IBD, aiming at providing evidence for clinical practice.

Keywords:  Crohn’s disease; gut microbiota; inflammatory bowel disease; probiotics; ulcerative colitis

DOI:  https://doi.org/10.3389/fmed.2025.1620079
mBio. 2025 Aug 18. e0134325

Antibiotics and phages drive region-specific diversity of OmpK36 in Klebsiella pneumoniae.

Guilhem Royer, Raphaël Laurenceau, Nicolas Cabanel, Benjamin Bardiaux, Karol Melissa Cerdas-Mejías, David Bikard, Isabelle Rosinski-Chupin, Philippe Glaser.

  The Enterobacterales outer membrane is impermeable to many antibiotics, but they can enter the cell via channel proteins, called porins. In Klebsiella pneumoniae, the porin OmpK36 is a major determinant of antibiotic resistance. Insertion of amino acids into the L3 constriction loop is frequently reported, leading to decreased channel size and reduced antibiotic susceptibility. While the involvement of the L3 loop in resistance is well-established, studies focused on a limited number of sequences, without considering any role for diversity outside L3. To fill this gap, we carried out a large-scale genomic comparison combined with experimental analysis. We analyzed 16,086 K. pneumoniae genomes to decipher the diversity of OmpK36 at the species level. We identified 385 protein variants classified into 7 main backbones, some associated with high-risk clones and, consequently, with major resistance classes. Comparison of predicted three-dimensional structures indicates variation in pore size depending on backbones. We constructed mutants carrying the main variants and compared their fitness and susceptibility to antibiotics and phages. Despite OmpK36 diversity and predicted pore radius differences, variations beyond the constriction loop do not seem to significantly impact antibiotic susceptibility and fitness. However, this diversity may have been partly shaped by phages targeting OmpK36, as evidenced by varying susceptibility to a T4-like phage depending on the backbones and the rapid acquisition of mutations in ompK36 among initially susceptible mutants following phage exposure. These findings suggest that while antibiotic pressure selects for L3 loop variations, phage predation may be a key driver of broader OmpK36 diversity.
IMPORTANCE: Porins are outer membrane proteins involved in the passive diffusion into the periplasm of substrates such as nutrients. They are also a major route for antibiotics. Mutations in the main porins of K. pneumoniae, OmpK35 and OmpK36, have been described and mainly lead to disruption of the former and a pore size reduction of the latter through amino acid insertion in the constriction loop. ompK36 mutations are clinically significant, with a reduction in susceptibility to β-lactams, particularly when strains also produce a carbapenemase. However, little is known about the overall diversity of OmpK36. Through large-scale genome analysis and experimental work, we sought to decipher the selective pressures that shape the diversity of this protein. Our results suggest that antibiotics are not the main driver of OmpK36 diversity at the level of the entire protein sequence and that phages can instead rapidly select variations in the extracellular loops.

Keywords:  OmpK36; antibiotic resistance; bacteriophages; genome analysis; porins

DOI:  https://doi.org/10.1128/mbio.01343-25
Infect Drug Resist. 2025 ;18 4023-4037

Knowledge, Attitudes and Practices of Healthcare Providers on Antibiotics Use and Resistance in Hospital Settings in Kinshasa, Democratic Republic of Congo.

Lionel Zawadi Mashami Bahinzi, Ben Bepouka, Celestin Nzanzu Mudogo, Alexis Sumbu Keya, Eric Musalu Mafuta, Junior Rica Matangila, Gauthier Kahunu Mesia, Hippolyte Nina Tuma Situakibanza, Octavie Metila Lunguya.

   Aim: The overall aim of this study is to assess the knowledge, attitudes and practices of healthcare providers regarding antibiotic therapy and bacterial resistance. Knowledge of antibiotic therapy was low (4.5/11 points). One hundred and eighteen respondents (27.5%) had taken part in at least one training course on rational antibiotic prescribing. One hundred seventy-five respondents (40.9%) took the results of the antibiogram into account when adapting antibiotic therapy when the results were available. There are deficiencies in antibiotic prescribing in Kinshasa/DRC.
Purpose: Inappropriate use of antibiotics is the main cause of antibiotic resistance worldwide. At the same time, the practice of prescribing antibiotics in Africa is not as well documented. The overall aim of this study is to assess the knowledge, attitudes and practices of healthcare providers regarding antibiotic therapy and bacterial resistance.
Participants and Methods: The KAP interview study was conducted from 2 December 2019 to 29 February 2020, among healthcare providers, in Kinshasa/DRC in 21 HZs including 25 General Reference Hospitals and the "Cliniques Universitaires de Kinshasa".
Results: Out of a sample of 430, with a participation rate of 99.6%. Knowledge of antibiotic therapy was low (mean score 4.5/11 points). As shown by the results on the treatment to be given in the event of upper respiratory tract infection (9.3%), then whether or not to reduce the dose of antibiotic in the event of renal failure (14.0%) and recognition of the local rate of resistance of Klebsiella spp. to ceftriaxone (12.6%). One hundred and eighteen respondents (27.5%) had taken part in at least one training course on rational antibiotic prescribing. One hundred seventy-five respondents (40.9%) took the results of the antibiogram into account when adapting antibiotic therapy when the results were available.
Conclusion: There are deficiencies in antibiotic prescribing in Kinshasa/DRC. The availability and use of microbiology services and training must be emphasized.

Keywords:  antibiotic therapy; attitudes; bacterial resistance; knowledge; practices

DOI:  https://doi.org/10.2147/IDR.S507753
Pharmacol Rep. 2025 Aug 19.

Real‑world safety and efficacy of biological agents in inflammatory bowel disease: a one-year post-marketing pharmacovigilance observational study in the Calabria region.

Antonio Fabiano, Caterina De Sarro, Domenico Frajia, Francesca Bosco, Lorenza Guarnieri, Stefano Ruga, Stefano Rodinò, Ladislava Sebkova, Enrico Ciliberto, Isidoro Buoncompagni, Laura Costantino, Antonio Leo, Gianmarco Marcianò, Vincenzo Rania, Rita Citraro, Ashour Michael, Giovambattista De Sarro.

   BACKGROUND: The use of immune-modifying biological agents has markedly changed the clinical course and the management of inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are essential for the early recognition of both expected and unexpected adverse events (AEs), providing a powerful tool for better defining the safety profiles of biologics in a real-world setting.
METHODS: Patients diagnosed with IBDs and treated with biologic drugs at two gastroenterology units in Calabria, Italy, were monitored during the period from 2023 to 2024. AEs and drug switches or swaps were recorded. The primary objective was to assess the safety profile of biological therapies in real-world practice, as measured by the occurrence of AEs. Secondary objectives focused on assessing treatment effectiveness by monitoring rates of therapeutic ineffectiveness and rigorously analyzing necessary modifications to therapy (swaps/switches) in response to treatment failure.
RESULTS: A total of 214 patients were enrolled, including 85 with Crohn's disease (CD) and 120 with ulcerative colitis (UC). Among biologics, vedolizumab (VDZ) was the most prescribed drug (50.3%), followed by ustekinumab (UST, 33.6%). Among biosimilars, infliximab (IFX) was the most administered (70%), followed by adalimumab (ADA) (63.3%). 96 patients experienced AEs, though no serious adverse events (SAEs) were reported. The highest number of AEs was reported with VDZ (n = 31; 32.3%), followed by IFX (n = 22, 23.0%), ADA and UST (n = 17, 17.7%), and golimumab (GOL) (n = 7; 7.3%). The biological drugs associated with the fewest AEs were upadacitinib (UPA) and tofacitinib (TFC) (n = 1; 1.0%).
CONCLUSIONS: This study confirms the importance of pharmacovigilance in monitoring the safety of biologics in IBDs. The results offer useful insights into the actual use of monoclonals in gastroenterology and support more targeted prescribing.
CLINICAL TRIAL NUMBER: Not applicable.

Keywords:  Adverse events (AEs); Biologics; Inflammatory bowel diseases (IBDs); Monoclonal antibodies; Pharmacovigilance; Post-marketing surveillance

DOI:  https://doi.org/10.1007/s43440-025-00774-x
Crit Rev Microbiol. 2025 Aug 20. 1-45

Biofilm-associated Escherichia coli infections: pathogenesis, clinical implications, and treatment strategies.

Damini Thakur, Lokender Kumar.

  Biofilm formation is a complex process in which bacteria adhere to surfaces and create a protective matrix. Biofilms shield bacteria, such as Escherichia coli, from antibiotics and the host immune system, greatly facilitating their pathogenesis by enabling immune evasion and antimicrobial resistance. This review examines the stages of E. coli biofilm formation and their role in infections across various body sites, including the central nervous system, eyes, ears, teeth, respiratory tract, cardiovascular system, gastrointestinal tract, urinary tract, and medical device-related infections. Each infection site is thoroughly analyzed in terms of clinical manifestations, diagnostic challenges, treatment resistance, and implications for patient management. Furthermore, this review discusses therapeutic advancements, which are crucial for combating biofilm-associated infections. By unraveling the complexities of biofilms and developing novel therapeutics, researchers and clinicians can enhance strategies for diagnosing, treating, and preventing persistent E. coli infections.

Keywords:  E. coli infections; biofilm formation; clinical significance; human health; pathogenesis

DOI:  https://doi.org/10.1080/1040841X.2025.2548490
NPJ Biofilms Microbiomes. 2025 Aug 16. 11(1): 163

Synergistic effects of commensals and phage predation in suppressing colonization by pathogenic Vibrio parahaemolyticus.

Ling Chen, Zhipeng Huang, Mathias Middelboe, Deng Deng, Yingfei Ma.

Colonization resistance is a fundamental mechanism by which microbiomes suppress pathogen invasion; however, the ecological and mechanistic determinants of its efficacy remain incompletely understood. Here, we constructed a defined microbial consortium and employed in vivo shrimp infection models to investigate the synergistic interaction between commensal microbes and a pathogen-specific phage in suppressing the pathogen Vibrio parahaemolyticus. Our in vitro experiment revealed that combining key taxa, particularly with phage integration, markedly enhanced pathogen exclusion. Furthermore, we demonstrated that establishing the consortium prior to pathogen exposure resulted in the irreversible suppression of pathogen proliferation, highlighting the critical importance of timing. Mechanistic analyses revealed that nutrient competition from commensals triggered prophage activation in the pathogen, thereby inhibiting its proliferation. Leveraging these insights, we rationally designed a minimalist, yet effective consortium that, when coupled with phage predation, consistently conferred robust colonization resistance in shrimp. This study delineates the core ecological principle underlying microbiota-mediated colonization resistance and establishes a tractable phage-commensal framework for pathogen control, with translational relevance in the context of rising antibiotic resistance in aquatic and potentially mammalian systems.

DOI: https://doi.org/10.1038/s41522-025-00802-x
ISME J. 2025 Aug 18. pii: wraf180. [Epub ahead of print]

Nitrogen availability shapes evolution of phage resistance in cyanobacteria.

Maimona Higazi, Dikla Kolan, Esther Cattan-Tsaushu, Zohar Freiman, Shira Ninio, Sarit Avrani.

  Nitrogen-fixing cyanobacteria play a key role in nitrogen and carbon biogeochemical cycles in aquatic ecosystems. Under nitrogen-limited conditions, their ability to fix nitrogen provides an advantage over other species and enables them to form harmful blooms, which are increasing in frequency and negatively impact aquatic environments. Cyanophages (viruses infecting cyanobacteria) impose strong selective pressures on these populations, and although cyanobacteria can rapidly evolve resistance to these phages, there is a tradeoff between phage resistance and nitrogen fixation. Therefore, it remains unclear whether nitrogen-fixing cyanobacteria can evolve resistance without compromising nitrogen fixation under bloom-inducing nitrogen starvation. Here, we explore the evolution of phage resistance in nitrogen-fixing cyanobacteria (Nostoc PCC 7120 and Cylindrospermopsis raciborskii) under nitrogen starvation. We found that phage-resistant strains evolved under nitrogen starvation, although resistance emerged more slowly than in nitrogen-rich environments. Whole-genome sequencing of 34 resistant strains revealed that mutations conferring resistance differed between nitrogen-rich and nitrogen-starved conditions. Nitrogen starvation selected for mutations predominantly in glycosyltransferase genes, which are associated with cell surface modifications. In contrast to resistant strains isolated under nitrogen-replete conditions, which exhibited impaired heterocyst formation, resistant strains selected under nitrogen starvation maintained their ability to form functional heterocysts and persist in nitrogen-limited environments. Our findings suggest that nitrogen availability influences the evolutionary trajectory of phage resistance, favoring mechanisms compatible with nitrogen fixation under nitrogen starvation. These results provide new insights into the ecological resilience of nitrogen-fixing cyanobacteria under phage predation, and demonstrate that nitrogen availability affects the cost of resistance, evolutionary trajectories and resistance mechanisms.

Keywords:  cost of resistance; cyanobacteria; genome evolution; glycosyltransferase; heterocyst; nitrogen fixation; phage; resistance; tradeoff

DOI:  https://doi.org/10.1093/ismejo/wraf180
Front Microbiol. 2025 ;16 1653368

Lytic bacteriophage disrupts biofilm and inhibits growth of pan-drug-resistant Listeria monocytogenes in dairy products.

Elsayed M Abdullah, Eman Y T Elariny, Rewan Abdelaziz, Abeer S Albalawi, Abeer M Almutrafy, Mohamed Samir A Zaki, Safaa A Abdel-Karim, Yasmine H Tartor.

  Listeria monocytogenes is a major foodborne pathogen whose presence presents a continuous challenge in the food industry. A key issue is the formation of biofilms, which are complex microbial communities that cling to surfaces. These biofilms are incredibly resilient, making them tough to eliminate and manage. Therefore, it is crucial to find new and innovative ways to prevent and remove them. This study investigated the prevalence of L. monocytogenes in raw milk and Kareish cheese samples, as well as its resistance to antimicrobials and its ability to form biofilms. We also isolated and characterized a lytic bacteriophage to explore its anti-biofilm potential. Listeria species prevalence was 20% (n = 24/120 samples), higher in raw milk (31.7%) than Kareish cheese (8.3%). Eighteen isolates (15%) were identified as L. monocytogenes. High resistance rates were observed, notably to cefotaxime and cotrimoxazole. One pan-drug resistant (PDR) isolate was found in Kareish cheese, and the other 17 isolates were multidrug resistant (MDR). All L. monocytogenes isolates formed biofilms, categorized as weak: n = 7, moderate: n = 9, and strong: n = 2. We isolated a lytic bacteriophage, vB_LmoP_M15, which demonstrated lytic activity against all L. monocytogenes isolates, including both MDR and PDR strains. This phage belongs to the Podoviridae family, characterized by a short, non-contractile tail and an icosahedral head. Its genome size was estimated to be approximately 48.5 kb based on agarose gel electrophoresis of undigested phage DNA using a high molecular weight marker, and its restriction pattern was analyzed using HinfI, HindIII, and HaeIII enzymes. It has a latent period of 15 min and a burst size of 172 phage particles per infected cell. Phage vB_LmoP_M15 demonstrated significant antibiofilm activity (p < 0.05 to p < 0.0001). It effectively disrupted preformed biofilms and inhibited biofilm formation by MDR/PDR isolates. Application of vB_LmoP_M15 in pasteurized milk resulted in a significant reduction of L. monocytogenes counts by 2.45 log10 CFU/ml over 7 days at 30°C. These findings underscore the significant potential of phage vB_LmoP_M15 for controlling L. monocytogenes contamination and biofilms in dairy products.

Keywords:  L. monocytogenes; anti-biofilm agents; bacteriophage; biocontrol; cheese; food safety; foodborne pathogens; milk

DOI:  https://doi.org/10.3389/fmicb.2025.1653368
BMJ Mil Health. 2025 Aug 18. pii: military-2025-002964. [Epub ahead of print]

Human augmentation to deliver an enhanced and resilient people capability for Defence.

Anna Casey, N Pattyn, K Hogenelst, N C Armstrong, Y Fonken, S L Kemp.

  From first tools, to flight, to advances in medicine and biotechnology, enhancing our innate abilities has been a constant goal and militaries the world over have long sought to advance the limits of human performance in their warfighters. Human augmentation (HA) encompasses a wide range of technologies that straddle a diversity of scientific disciplines and maturity levels, including wearable assistive technologies such as exoskeletons, neurotechnology, pharmacology, telexistence and genetics. Recent and rapid advances in life sciences and biotechnology and the convergence of fields such as artificial intelligence, robotics and medicine present us with a radically different opportunity for optimising and enhancing human performance. HA can be considered a potentially important strategy underpinning our ability to fight and win wars, by making soldiers more lethal and better able to survive. This paper is based on the HA thematic session held at the 6th International Congress on Soldiers' Physical Performance (ICSPP) in London in 2023. It considers aspects of HA of interest to participating nations and provides a state-of-the-art review of HA from a military perspective by experts engaged in this area. It considers the development of capability requirements, ethical, legal and social aspects and candidate HA technologies, one with ancient roots but modern applications for Defence (pharmacological augmentation) and one emerging area (non-invasive brain stimulation). HA offers a number of benefits, opportunities and challenges to the Defence community. Deployment of these technologies must take place within the boundaries of a nation's core values and beliefs, the rules-based international order and the freedoms that underpin their militaries' moral and ethical foundations.

Keywords:  CLINICAL PHARMACOLOGY; Military Personnel; Neurobiology; Physiology

DOI:  https://doi.org/10.1136/military-2025-002964
Mater Today Bio. 2025 Oct;34 102160

Delivered baicalein immunomodulatory hydrogel with dual properties of pH-responsive and anti-infection orchestrates pro-regenerative response of macrophages for enhanced hypertrophic scars therapy.

Fengqing Shang, Yanling Qu, Yu Li, Lingjuan Dong, Dan Liu, Zhe Wang, Afeng Li, Yinghui Li, Dan Zhang, Leiguo Ming, Ronghua Jin.

  Antibiotic-resistant bacterial infections in skin wounds can cause persistent inflammatory responses, which may lead to severe hypertrophic scarring. In this study, a pH-responsive antibacterial hydrogel composed of phenylboronic acid-grafted chitosan (PBCS) and tannic acid (TA) was developed to achieve controlled and long-lasting release of baicalein (BA) to address the critical challenges of bacterial infection, wound healing, and scarring. The composite hydrogel (BA@PBCS-TA) not only demonstrates excellent injectability, self-healing properties, and robust mechanical performance but also exhibits favorable biological characteristics. Through pH-responsive release of BA, it effectively eliminates Methicillin-resistant Staphylococcus aureus (MRSA). In vivo experiments further confirm its ability to significantly inhibit fibroblast activation and reduce abnormal collagen deposition, effectively preventing excessive scar formation. Additionally, network pharmacology has identified Glycogen Synthase Kinase 3 Beta (GSK3β) as a key target for BA in inhibiting hypertrophic scar formation. Cellular experiments further demonstrate that the BA@PBCS-TA hydrogel can suppress GSK3β expression, activate the Wnt/β-catenin signaling pathway to repolarize macrophages into the M2 phenotype, and exhibit significant immunomodulatory effects. These results highlight the BA@PBCS-TA hydrogel's ability to harness the excellent properties of biomaterials and optimize BA's pharmacological effects, ultimately promoting wound healing and offering a strategic solution for scar reduction.

Keywords:  Bacterial infection; Baicalein; GSK3β; Hydrogel; Hypertrophic scars; M2 macrophage

DOI:  https://doi.org/10.1016/j.mtbio.2025.102160
Chem Commun (Camb). 2025 Aug 18.

Controlling nanocage assembly, towards developing a one-health "plug & play" platform for targeted therapy.

Yujie Sheng, Mark J Sutton, Kourosh H Ebrahimi.

There is a growing interest in developing one-health "plug and play" platforms for making different therapeutics/prophylactics to target various biological entities such as viruses, cancer cells, or bacteria. Such a platform could benefit from advances in artificial intelligence (AI) for sustainable manufacturing. In this respect, naturally occurring protein nanocages, such as iron-storage protein ferritin, are emerging as ideal candidates for various applications in nanomedicine. However, the spontaneous self-assembly of these naturally occurring nanocages has been a bottleneck for their application as a one-health "plug and play" platform. In this review, we will take a fresh look at the application of natural protein nanocages in nanomedicine by discussing our current understanding of their self-assembly process. We highlight our recent progress in engineering ferritin subunits to create a one-health "plug and play" platform technology to develop various therapeutic or prophylactic nanomedicines. We will discuss the advantages of this technology, its implications for understanding nanocage assembly, and potential future application areas.

DOI: https://doi.org/10.1039/d5cc03592a
Front Med (Lausanne). 2025 ;12 1615753

Research trends and topics on sepsis immunosuppression: a bibliometric and visual analysis of global research from 2004 to 2024.

Ji Yin, Yantong Wan, Guangqin Chen, Nanhong Li, Fei Liu, Haihua Luo, Yijing Li, Shan Li, Yong Jiang.

   Background: Sepsis, a condition characterized by critical organ impairment resulting from dysregulated response to infection, remains a leading cause of mortality globally. Immunosuppression significantly dictates the clinical trajectory and ultimate prognosis in sepsis. Research on sepsis-related immunosuppression has gained substantial attention in recent years. However, a comprehensive and objective analysis of the current state of research remains scarce. This study employs bibliometric techniques and knowledge mapping to provide a visual analysis of trends and developments in sepsis immunosuppression, offering a systematic overview for researchers in the field.
Objectives: This study aims to: (1) Quantitatively characterize global publication trends, key contributors (countries/institutions/journals/authors), and collaborative networks in sepsis immunosuppression research (2004-2024); (2) Identify current hotspots and future directions in this field.
Materials and methods: Articles and reviews related to sepsis immunosuppression were sourced from the Web of Science Core Collection via subject-specific searches. Bibliometric analyses were executed using Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Studio's R-Tool).
Results: From January 1, 2004, to March 22, 2024, 3,082 articles on sepsis immunosuppression authored by 16,545 individuals across 116 institutions from 30 countries were identified. Collaborative network analysis highlights the United States as the leading contributor, with key institutions including the University of Florida and Washington University. Strong international collaboration is evident, particularly between the United States and China, as well as the United States and Germany. Frontiers in Immunology emerged as the most prolific journal, while Journal of Immunology garnered the highest co-citation frequency. Guillaume Monneret has published the greatest number of relevant articles, while Richard S. Hotchkiss is the most frequently co-cited author. The research predominantly focuses on immunology, molecular biology, and clinical treatments. Keyword analysis suggests that immune cells, cell death, and personalized clinical treatments are emerging research hotspots in the field.
Conclusion: This bibliometric analysis maps evolving trends and forecasts emerging hotspots in sepsis immunosuppression research, providing direction for future studies.

Keywords:  bibliometric analysis; clinical treatment; immunoparalysis; immunosuppression; sepsis

DOI:  https://doi.org/10.3389/fmed.2025.1615753
bioRxiv. 2025 Aug 14. pii: 2025.08.14.669717. [Epub ahead of print]

Unmasking Pathogen Traits for Chronic Colonization in Neurogenic Bladder Patients.

Seth A Reasoner, Brendan T Frainey, Owen F Hale, Alexandra Borden, M Kyle Graham, Elise Turner, Lucas R Brenes, Carl B W Soderstrom, Hamilton Green, Jonathan E Schmitz, Michael T Laub, Maryellen S Kelly, Douglass B Clayton, Maria Hadjifrangiskou.

Individuals with neurogenic bladder are particularly susceptible to both chronic bacterial colonization of the bladder and urinary tract infections (UTIs). Neurogenic bladder can arise from a variety of diseases such as diabetes, spinal cord injuries, and spina bifida. To study the ecological and evolutionary dynamics of the microbiome in neurogenic bladder, we developed a longitudinal cohort of 77 children and young adults with spina bifida from two medical centers. We used enhanced urine culture, 16S rRNA sequencing, and whole genome sequencing to characterize the microbial composition of urine and fecal samples. In addition to prospective sample collection, we retrieved prior bacterial isolates from enrolled patients from Vanderbilt's clinical microbial biobank, MicroVU. This allowed us to compare bacterial isolates from the same patients over a period of five years. Urine samples were characterized by high abundance of urinary pathogens, such as E. coli and Klebsiella . From longitudinal isolates from individual patients, we identified two common patterns of urinary tract colonization. We observed either the rapid cycling of strains and/or species, often following antibiotic treatment, or we observed the persistence of a single strain across timepoints. Neither persistence of a strain nor colonization with a new strain or species was associated with increased antibiotic resistance. Rather, in paired longitudinally collected strains from the same patients, mutations were identified in genes that code for cell envelope components associated with immune or phage evasion. Experimental testing revealed that O-antigen/LPS biosynthesis mutations confer protection from the immune system while altering susceptibility to phage predation, reflecting a fitness trade-off. We argue that this unparalleled cohort offers the opportunity to identify mechanisms of bacterial adaptation to the urinary tract that can be exploited in future therapeutic approaches.

DOI: https://doi.org/10.1101/2025.08.14.669717
bioRxiv. 2025 Aug 11. pii: 2025.08.10.669567. [Epub ahead of print]

A prevalent huge phage clade in human and animal gut microbiomes.

LinXing Chen, Antonio Pedro Camargo, Yiting Qin, Eugene V Koonin, Haoyu Wang, Yuanqiang Zou, Yi Duan, Hao Li.

Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (Jumbo gut) phages with genomes of 360-402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38-57% identity, suggesting horizontal acquisition from other phages. Over 1,500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.

DOI: https://doi.org/10.1101/2025.08.10.669567