bims-fagtap 2025-09-21 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–09–21
twenty-six papers selected by
Luca Bolliger, lxBio

Microbial keratitis in the age of resistance: unlocking the therapeutic potential of phage therapy.
The joint action of antibiotics, bacteriophage, and the innate immune response in the treatment of bacterial infections.
Evaluating phage lytic activity: from plaque assays to single-cell technologies.
Phage therapy for environmental biotechnology applications.
Efficacy of precisely tailored phage cocktails targeting carbapenem-resistant Acinetobacter baumannii reveals evolutionary trade-offs: a proof-of-concept study.
Next-generation antimicrobials: A review of phage lysins as precision weapons against drug-resistant pathogens.
Phage therapy and its role in cancer treatment and control.
Gut Virome and Aging: Phage-Driven Microbial Stability and Immune Modulation.
LicD-mediated cell wall decoration governs phage sensitivity in Enterococcus faecalis clinical isolates.
Understanding Bacterial Antiviral Defence Systems and Phage Receptors to Better Inform Rational Phage Cocktail Design to Treat Bacterial Canker.
Phages with a broad host range are common across ecosystems.
Cracking the Code: How Nano-Informatics is Crafting Intelligent Nano-Weapons to Outsmart Multiple Drug Resistance (MDR).
Bacteriophage and Fusidic Acid Have Synergistic Effect Against Meticillin-Resistant Staphylococcus pseudintermedius in Ex Vivo Canine Dermis Model.
Bacteria-mediated cancer therapy (BMCT): Therapeutic applications, clinical insights, and the microbiome as an emerging hallmark of cancer.
The bacteriophage T4 homologous recombination system: mechanism, applications, conservation, and environmental significance.
Metagenomic Sequencing Reveals Distinct Gut Microbiome Profiles in Therapy-Naïve de Novo Pediatric Inflammatory Bowel Disease.
Characterization of a Novel Phage HZJ33 and Its Application in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection.
Fungal infections in focus: accelerating non-invasive imaging from preclinical insights to clinical breakthroughs.
Wound Care Knowledge of Community Pharmacists and Pharmacy Staff: A Cross-Sectional Survey.
Decolonisation and approaches to this for preventing surgical site infection.
Systematic Review on the Role of Microfluidic Platforms in Advancing Scalable and Precise Microbial Bioprocessing.
Phage-based decontamination: Exploring resistance, disinfectant tolerance, and virulence trade-offs in Acinetobacter baumannii.
Biomaterials strategy for promoting palatal wound healing.
Promotion of infected wound healing by black phosphorus-strontium via photothermal therapy.
Resveratrol in Dermatological Therapy: A Critical Review of Mechanisms, Delivery Innovations, and Clinical Frontiers.
Draft genome sequence and intact prophage characterisation of multidrug-resistant Acinetobacter baumannii isolate ABU3 from a tracheal suction specimen in Thailand.

Graefes Arch Clin Exp Ophthalmol. 2025 Sep 18.

Microbial keratitis in the age of resistance: unlocking the therapeutic potential of phage therapy.

Rafwana Ibrahim, Pritam Kumar, Jesil Mathew Aranjani.

  Keratitis an inflammatory disorder of the corneal tissue, poses a significant threat to vision and, if left untreated, can even progress to irreversible blindness. Clinical manifestations of the disease include ocular redness, pain, photophobia, excessive tearing, and visual disturbances, with severe cases often leading to corneal ulceration, scarring, or perforation. The global prevalence of keratitis exhibits substantial geographical variability, largely influenced by access to healthcare, environmental factors, and behavioral risk determinants, most notably, the use of contact lenses. In recent years, microbial keratitis (MK) has shown a concerning rise in incidence, particularly among contact lens users, frequently attributed to improper lens hygiene and extended wear. Current therapy mainly depends on the intensive use of topical antimicrobial agents; however, the emergence of multidrug-resistant (MDR) pathogens and the protective nature of biofilms significantly compromise therapeutic efficacy and efficiency. These limitations pave the way to the urgent need for alternative strategies. Bacteriophage therapy, which was in use even before the development of antibiotics, regained interest as a precision-based antibacterial treatment that is capable of selectively targeting pathogenic bacteria, including MDR strains, without disrupting the native ocular microbiota or damaging host tissue. This review explores the different types of keratitis and pathogenesis, highlights the problems related to conventional therapies, and emphasizes the potential of phage therapy as a novel, adjunctive, or standalone intervention.

Keywords:  Antibiotic resistance; Biofilm; Global health; Microbial keratitis; Novel drug delivery; Phage therapy

DOI:  https://doi.org/10.1007/s00417-025-06961-z
Front Microbiol. 2025 ;16 1632267

The joint action of antibiotics, bacteriophage, and the innate immune response in the treatment of bacterial infections.

Brandon A Berryhill, Teresa Gil-Gil, Bruce R Levin.

  Studies of antimicrobial therapeutics have traditionally neglected the contribution of the host in determining the course of treatment and its outcome. One critical host element, which shapes the dynamics of treatment is the innate immune system. Studies of chemotherapeutics and complementary therapies such as bacteriophage (phage), are commonly performed with mice that purposely have an ablated innate immune system. Here, we generate a mathematical and computer-simulation model of the joint action of antibiotics, phage, and phagocytes. Our analysis of this model highlights the need for future studies to consider the role of the host's innate immune system in determining treatment outcomes. Critically, our model predicts that the conditions under which resistance to the treatment agent(s) will emerge are much narrower than commonly anticipate. We also generate a second model to predict the dynamics of treatment when multiple phages are used. This model provides support for the application of cocktails to treat infections rather than individual phages. Overall, this study provides hypotheses that can readily be tested experimentally with both in vitro and in vivo experiments.

Keywords:  Innate immunity; antibiotic resistance; antibiotics; bacteriophages; infection dynamics; mathematical and computer-simulation modeling; phage resistance

DOI:  https://doi.org/10.3389/fmicb.2025.1632267
Front Microbiol. 2025 ;16 1659093

Evaluating phage lytic activity: from plaque assays to single-cell technologies.

Vladimir Panteleev, Andrey Kulbachinskiy, Daria Gelfenbein.

  Bacteriophages are the most abundant biological entities on Earth, playing critical roles in microbial ecology, evolution, and horizontal gene transfer. Since the discovery of bacteriophages in the early 20th century, a wide range of techniques has been developed to study their lytic activity. This review provides a perspective on the wide range of methods for studying phage-bacteria interactions, spanning classical bulk-culture techniques and modern single-cell and high-throughput approaches. The first section covers solid culture methods relying on plaque formation phenomenon, which allow for quantification of infectious viruses, phage host-range establishment, and analysis of certain phage traits, now augmented by robotic high-throughput screening. The second section focuses on liquid culture approaches, utilizing optical density measurements, quantitative PCR, metabolic assays and cell damage assays to measure the infection dynamics. The third section details single-cell techniques, which help to dissect the heterogeneity of infection within cell populations, using microscopy, microfluidics, next-generation sequencing, and Hi-C methods. The integration of these diverse methods has greatly advanced our understanding of the molecular mechanisms of phage infection, bacterial immunity, and facilitated phage therapy development. This review is dedicated to the 110th anniversary of phage discovery and is aimed to guide researchers in selecting optimal techniques in the fast-growing field of phage biology, phage-host interactions, bacterial immunity, and phage therapy.

Keywords:  bacteriophage plaques; bacteriophages; lytic cycle; single cell methods; viral infection

DOI:  https://doi.org/10.3389/fmicb.2025.1659093
Front Microbiol. 2025 ;16 1621103

Phage therapy for environmental biotechnology applications.

Suniti Singh, Rachel Samson, Francis Hassard.

  Environmental compartments, from soils and crop rhizospheres, to bio-reactors and municipal water networks have emerged as dynamic hot-spots for antimicrobial-resistance evolution and dissemination. Bacteriophages offer a precision, self-amplifying alternative to conventional biocides, yet their environmental deployment, intellectual-property space and commercial readiness remain only partially charted. Here, we critically synthesize the past decade of progress in phage-based interventions across three sectors: (i) soil remediation and crop-protection interfaces, where multi-phage cocktails suppress wilt- and blight-causing pathogens while preserving beneficial microbiota; (ii) biofuel and petro-energy infrastructures, in which lytic phages mitigate the microbiologically influenced corrosion and contaminated fermentations, restoring ethanol yields; and (iii) natural and engineered water systems, where phages show promise in treating recalcitrant biofilms, algal blooms and selectively ablate World Health Organization-priority pathogens. Meta-analysis of the World Intellectual Property Organization database reveals rapidly rising but geographically skewed patent activity, with China and the United States accounting for >61% of reviewed filings, and a gap between laboratory proof-of-concepts and marketed products. We identify bottlenecks, including lack of good manufacturing practice at scale, fragmented regulatory frameworks, and the evolutionary balance between single-phage precision and cocktail breadth. A roadmap is suggested that couples high-throughput phage discovery, synthetic tailoring and adaptive approval pathways. Together, these advances position environmental phage therapy to become a cornerstone of the One-Health response to increasing levels of microbial resistance.

Keywords:  biofuel system; engineered water system; patent landscape; phage therapy; soil-vegetable system

DOI:  https://doi.org/10.3389/fmicb.2025.1621103
EBioMedicine. 2025 Sep 18. pii: S2352-3964(25)00386-X. [Epub ahead of print]120 105942

Efficacy of precisely tailored phage cocktails targeting carbapenem-resistant Acinetobacter baumannii reveals evolutionary trade-offs: a proof-of-concept study.

Ziqiang Liu, Xin Tan, Min Xiong, Shitong Lu, Yongqing Yang, Heng Zhu, Jieqiong Zhang, Xiangying Luo, Caiyun Zhou, Shujiang Wei, Ning Zhou, Xueyan Liu, Changqing Bai, Yongjun Pan, Yingfei Ma.

   BACKGROUND: The rapid emergence of phage-resistant bacterial mutants and the challenge of developing tailored phage cocktails have significantly hindered the broad application of phage therapy. This is particularly critical for infections caused by highly prevalent strains such as capsule locus 2 (KL2)-type carbapenem-resistant Acinetobacter baumannii (CRAB) in China.
METHODS: We employed an iterative phage adaptive selection (iPAS) strategy to develop an optimised phage cocktail specifically targeting KL2-type CRAB strains. To facilitate efficient clinical application, we also established a rapid identification method for KL2-type isolates. The efficacy and safety of this rationally designed cocktail were subsequently evaluated in a clinical setting through its application in two compassionate use cases of CRAB infection as a proof-of-concept study. Whole genomic sequencing was conducted on the isolated phage-resistant mutants to reveal the related mutations.
FINDINGS: KL2-type A. baumannii was the predominant lineage, accounting for 17.7% (159/896) of isolates reported across China over the past five years, and 33.3% (46/138) of clinical CRAB isolates obtained by our laboratory from five hospitals and one institute in Guangdong Province. The optimised phage cocktail effectively targeted 89.1% (41/46) of these KL2-type isolates. The phage-resistant A. baumannii mutants exhibited beneficial trade-offs, including increased antibiotic sensitivity, reduced virulence, susceptibility to immune clearance, and impaired biofilm formation. Genomic analysis revealed that these trade-offs were driven by concentrated and consistent mutations in genes involved in lipo-oligosaccharide and capsular polysaccharide biosynthesis. Crucially, the application of this cocktail in two clinical cases of CRAB infection demonstrated both clinical efficacy in resolving infections and a favourable safety profile.
INTERPRETATION: This research underscores the potential of rational tailored phage cocktails developed through strategies like iPAS, to address the growing threat of CRAB infections. The successful clinical application highlights the translational impact of this study. Furthermore, the study provides valuable insights into the co-evolutionary dynamics between bacteria and phages, paving the way for broader and more effective clinical applications of phage therapy.
FUNDING: This work was supported by National Key R&D Programme of China; Shenzhen Medical Research Funds; Shenzhen Nanshan District Health Technology Major Project; Shenzhen Science and Technology Innovation Commission and Shenzhen Science and Technology Programme.

Keywords:  KL-2 type carbapenem-resistant Acinetobacter baumannii; Phage therapy; Tailored phage cocktail; Trade-offs

DOI:  https://doi.org/10.1016/j.ebiom.2025.105942
Virulence. 2025 Dec;16(1): 2562634

Next-generation antimicrobials: A review of phage lysins as precision weapons against drug-resistant pathogens.

Xinge Cui, Luwei Chai, Yongkang Zhang, Yangwei Pan, Hongbing Liu, Xianlu Lei, Tao Le.

  The escalating misuse of antibiotics has precipitated a dramatic rise in bacterial drug resistance, rendering conventional therapies increasingly ineffective. In this post-antibiotic era, phage lysins have emerged as a novel class of antimicrobial agents, attracting significant attention for their precise targeting of drug-resistant pathogens. Despite promising preclinical results - highlighting their rapid bactericidal efficacy and synergistic potential with other antimicrobials - the clinical translation of lysins remains limited by unresolved challenges related to efficacy, safety, pharmacokinetics, and dosing optimization. This review provides a comprehensive overview of lysin research advancements, discusses diverse application strategies, and critically evaluates therapeutic outcomes from animal models and early clinical trials. Additionally, it addresses the key obstacles impeding lysin development and proposes practical solutions and future research directions to unlock the full clinical potential of this innovative antimicrobial strategy.

Keywords:  Phage; antibiotic resistance; antimicrobial resistance; combination therapy; phage lysin; phage therapy

DOI:  https://doi.org/10.1080/21505594.2025.2562634
Folia Microbiol (Praha). 2025 Sep 17.

Phage therapy and its role in cancer treatment and control.

Heba Ibrahim Abd El-Moaty, Ahmed S Doghish, Hebatallah Ahmed Mohamed Moustafa, Wagiha S Elkalla, Ghadir A Sayed, Nourhan H Elshami, Sherif S Abdel Mageed, Osama A Mohammed, Mahmoud A Elrebehy, Kareem AlFarsi, Amr M Abdelfatah, Aly M Waseem, Ahmed O Abdulkader, Rabab S Hamad, Akram N Salah.

  Cancer is very dangerous and has a high death rate around the world. This rate is expected to rise even more in the next few years. Chemotherapy and radiation therapy are two examples of current treatment choices. However, they have some problems, such as side effects, being less effective overall, being expensive, and not being widely available. A rising demand exists for alternative therapies that can specifically target cancer cells while minimizing adverse effects. Phage has a dual function as both a diagnostic and therapeutic instrument. This phage has the potential to serve as a suitable recombinant medicine, potentially replacing current labor-intensive, high-capital therapies that often lead to failure or severe adverse effects. Identifying tumor-homing peptides constitutes one of the most substantial hurdles. This therapeutic approach is crucial in tumor treatment, demonstrating remarkable precision and efficacy regardless of the target site. Phages, which target bacteria but not eukaryotic cells, have arisen as viable cancer therapies owing to their distinctive attributes, such as selectivity and simplicity of genetic modification. Engineered phages have the potential to revolutionize cancer therapy by selectively targeting malignant cells while preserving healthy ones. Bacteriophages are presently utilized extensively in several fields of science and medicine, with cancer therapy being the most compelling application. While challenges remain, especially in identifying the most effective tumor-targeting peptides, research increasingly supports the safety and effectiveness of phage-based therapies in cancer treatment. This review highlights recent progress and ongoing challenges in the use of phage therapy for cancer.

Keywords:  Biomedicine; Cancer; Drug delivery vehicle; Phage therapy; Phage-based medicine

DOI:  https://doi.org/10.1007/s12223-025-01342-9
Aging Dis. 2025 Sep 07.

Gut Virome and Aging: Phage-Driven Microbial Stability and Immune Modulation.

Kaleem Ullah, Rabia Kanwar, Saqib Ali, Saif Uddin, Izza Izza, Irfan Ahmad, Khalid J Alzahrani, Abdul Qadeer, Chun-Ting Chu, Chien-Chin Chen.

The gut harbors trillions of microbes that play essential roles in metabolism and immunological functions. The virome, an important but understudied component of the gut microbiota, comprises bacteriophages commonly referred to as bacterial viruses, among other inhabitants. Understanding the interplay between the gut virome and bacteria can illuminate the dynamics of microorganisms in both healthy and diseased states. This knowledge can open new avenues for treatment, such as phage therapy and microbiota modulation, which aim to restore balance in the gut and improve overall health. The composition and diversity of the gut microbiome and virome undergo significant changes, which have been linked to increased susceptibility to infections, chronic inflammation, and age-related disease. Exploring the gut virome's role in aging may provide insights into how viral and bacterial interactions influence immune senescence and gut resilience in the elderly population. This review provides an overview of the current understanding of the relationship between the gut virome, specifically phages associated with gut bacteria, and mechanisms of phage-host interactions, shedding light on how these factors affect and influence communities. Additionally, this review also explores the impact of the gut virome on gut resilience and its role in shaping and influencing the host's immune response. Maintaining a healthy gut requires a stable and robust virome. Therefore, future research on the virome is crucial for the development of microbe-based products that enhance human and animal health and aid in addressing specific diseases.

DOI: https://doi.org/10.14336/AD.2025.0854
Microbiol Res. 2025 Sep 12. pii: S0944-5013(25)00300-3. [Epub ahead of print]302 128341

LicD-mediated cell wall decoration governs phage sensitivity in Enterococcus faecalis clinical isolates.

Muhammed Awad, George Bouras, Sholeh Feizi, Susanna R Grigson, Peter-John Wormald, Alkis J Psaltis, Sarah Vreugde.

  Enterococcus faecalis has emerged as a prevalent antibiotic-resistant pathogen in clinical settings. Herein, we report the identification of three novel lytic phages targeting vancomycin-resistant E. faecalis. While the isolated phages all belonged to the Kochikohdavirus genus, there were distinctive differences in their tail fibre proteins, affecting their adsorption. The phages showed strong antibacterial activity with wide host range, infecting > 90 % of the tested E. faecalis clinical and hospital wastewater isolates (n = 13) with variable efficiency. The variation in host range was genomically correlated to the presence of the licD gene in phage sensitive bacteria, which is responsible for phosphorylcholine decoration of the bacterial cell wall. Furthermore, the isolated phages were predicted to harbour genes encoding for depolymerase enzymes, which was confirmed by in vitro testing showing a > 80 % reduction in biofilm biomass. Phages inhibited bacterial growth for ≥ 12 h, followed by the emergence of bacteriophage insensitive mutants (BIMs) that were 4-fold more sensitive to vancomycin compared to parent strains. In addition, the isolated BIMs showed less capability of evading THP-1 macrophage and produced weaker biofilms. These findings underpin the potential of the isolated phages in combating recalcitrant E. faecalis associated biofilm-mediated infections.

Keywords:  Antibiotic resistance; Biofilms; Depolymerase; Enterococcus faecalis; Phage therapy; Phosphoryl choline

DOI:  https://doi.org/10.1016/j.micres.2025.128341
Microb Biotechnol. 2025 Sep;18(9): e70232

Understanding Bacterial Antiviral Defence Systems and Phage Receptors to Better Inform Rational Phage Cocktail Design to Treat Bacterial Canker.

Kieran Cooney-Nutley, Sneha Chakravorty, Imogen Nix, Ziyue Zeng, Shannon F Greer, Mojgan Rabiey.

  Pseudomonas syringae is a plant pathogen complex responsible for bacterial canker in cherry. In the absence of any control measures, bacteriophages (phages) have the potential for biocontrol. However, it is crucial to first evaluate the role of bacterial antiviral defence systems (ADS) in phage infection dynamics for careful design of a phage cocktail (mixture). Investigating 250 Pseudomonas strains revealed the Ps complex possessed diverse ADS with defence profiles being influenced by phylogeny. Phage host range assays revealed five MR phages with distinct genotypes possessed strong lytic activity against several bacterial canker-causing Ps pathovars, including syringae and morsprunorum race 1 and 2. Phage susceptibility and resistance appeared to be associated with individual ADS rather than defence profiles as a whole. Multisequence alignment of lipopolysaccharide biosynthesis genes glucose-1-phosphate thymidylyltransferase (gpt), glycosyltransferase family 1 (gst1) and lipopolysaccharide kinase (lpk) found these potential receptor genes to be highly conserved within Ps phylogroups. However, gpt alone appeared to influence phage infectivity. Our findings indicate that the gpt gene is a potential primary predictor of MR phage susceptibility, hypothesised to influence phage absorption, while individual ADS only have a secondary role in phage resistance. This study highlights that understanding the genetic mechanisms underlying phage-bacterial interactions is crucial for designing more effective phage cocktails capable of targeting a broader range of pathogenic strains, but phage screening still is a powerful tool to select phages for biocontrol treatments.

Keywords:   Prunus avium ; Pseudomonas syringae ; antiviral defence system; bacteriophage; host range; lipopolysaccharide

DOI:  https://doi.org/10.1111/1751-7915.70232
Nat Microbiol. 2025 Sep 19.

Phages with a broad host range are common across ecosystems.

Amaury Bignaud, Devon E Conti, Agnès Thierry, Jacques Serizay, Karine Labadie, Julie Poulain, Olivia Cheny, Maritrini Colón-González, Laurent Debarbieux, Marianna Guerrero-Osornio, Sophie Helaine, Peter Hill, Gwenaelle Le Tinier, Gael A Millot, Lucia Morales, Andrés Parada, Nadia Riera, Gregorio Iraola, Romain Koszul, Martial Marbouty.

Phages are diverse and abundant within microbial communities, where they play major roles in their evolution and adaptation. Phage replication, and multiplication, is generally thought to be restricted within a single or narrow host range. Here we use published and newly generated proximity-ligation-based metagenomic Hi-C (metaHiC) data from various environments to explore virus-host interactions. We reconstructed 4,975 microbial and 6,572 phage genomes of medium quality or higher. MetaHiC yielded a contact network between genomes and enabled assignment of approximately half of phage genomes to their hosts, revealing that a substantial proportion of these phages interact with multiple species in environments as diverse as the oceanic water column or the human gut. This observation challenges the traditional view of a narrow host spectrum of phages by unveiling that multihost associations are common across ecosystems, with implications for how they might impact ecology and evolution and phage therapy approaches.

DOI: https://doi.org/10.1038/s41564-025-02108-2
Pharm Nanotechnol. 2025 Sep 12.

Cracking the Code: How Nano-Informatics is Crafting Intelligent Nano-Weapons to Outsmart Multiple Drug Resistance (MDR).

Priyanka Sinoliya, Ravi Ranjan Kumar Niraj, Vinay Sharma.

   INTRODUCTION: Multiple Drug Resistance (MDR) is one of the prime concerns globally in the health sector. The emergence and proliferation of ESKAPE pathogens, along with drug resistance in cancer cells, represent a significant challenge to public health, emphasizing the need for novel therapeutics, improved infection control practices, and ongoing research to understand and combat antibiotic resistance. Addressing multiple drug resistance involves several modern therapeutic strategies, such as phage therapy, immunotherapy, combinatorial therapy, and more. Advanced diagnostic tools, effective control measures, and stringent regulatory and policy initiatives raising public awareness are also crucial.
METHODS: This study scouted computational approaches, focusing on their application in nanotechnology and nano-drug systems in clinical settings. A systematic approach was employed to gather, screen, and critically analyze the relevant literature for this review.
RESULTS: This study found that various tools and databases are evolving for reconnaissance in the field of nano-informatics, which will lead to research and development.
DISCUSSION: This study highlights the rapid advancement of nano-informatics tools and databases, which are crucial for advancing computational approaches in nanomedicine and therapeutic research. These emerging resources support predictive analysis and integration with biological datasets, though challenges remain in data standardization, accessibility, and interoperability across platforms.
CONCLUSION: To mitigate multiple drug resistance, researchers are exploring various approaches, and nano-informatics can provide new insight into dealing with it. This approach will advance the development of medical devices, drug design, and delivery systems.

Keywords:  Nanotechnology; antimicrobial drugs; drug delivery system.; in-silico approaches; multiple drug resistance; nanodrugs

DOI:  https://doi.org/10.2174/0122117385383102250818052847
Vet Dermatol. 2025 Sep 18.

Bacteriophage and Fusidic Acid Have Synergistic Effect Against Meticillin-Resistant Staphylococcus pseudintermedius in Ex Vivo Canine Dermis Model.

Sarah Ehling, Elisa Peh, Hilke Oltmanns, Jessica Meissner, Sophie Kittler, Christina Puff, Jutta Verspohl, Mathias Müsken, Madeleine Plötz, Andrea Vanessa Volk.

   BACKGROUND: Antimicrobial stewardship has become vital given the progressive emergence of multidrug-resistant bacteria, and novel approaches to the treatment of bacterial infections are needed. Recently, reported synergistic effects of antibacterial drugs and bacteriophage therapy have revealed promising applications for the management of meticillin-resistant staphylococcal infections.
OBJECTIVES: The objective of this study was to investigate the response of meticillin-resistant Staphylococcus pseudintermedius (MRSP) to treatment with a newly isolated, lytic MRSP-specific bacteriophage. Furthermore, a postulated synergism between phage and fusidic acid was examined in a canine ex vivo dermis model.
MATERIAL AND METHODS: Skin was harvested from the lateral thorax of a euthanised dog, clipped, the subcutis removed, and epidermis cleaved via a modified salt-split technique. The ex vivo dermis model established in Franz diffusion cells was inoculated with 1 × 107 colony-forming units (cfu) of a clinical MRSP strain for 16 h. Then, experimental groups were treated with phage vB_SpsS_LmqsKl44-4 at a concentration of 2 × 106 plaque-forming units and fusidic acid 0.4 mg alone or in combination for an additional 8 h.
RESULTS: Histopathological results showed that colonies of MRSP reached the superficial dermis and entered hair follicles. Co-treatment with fusidic acid and phage significantly reduced the amount of MRSP after 8 h.
CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, topical co-treatment with fusidic acid and a phage could be a promising approach to the treatment of canine MRSP pyoderma.

Keywords:  Franz diffusion cells; bacteriophage (phage); canine ex vivo dermis model; meticillin‐resistant Staphylococcus pseudintermedius

DOI:  https://doi.org/10.1111/vde.70030
Biomed Pharmacother. 2025 Sep 17. pii: S0753-3322(25)00753-X. [Epub ahead of print]192 118559

Bacteria-mediated cancer therapy (BMCT): Therapeutic applications, clinical insights, and the microbiome as an emerging hallmark of cancer.

Mrunali Jayaprakash, Deekshit Vijaya Kumar, Gunimala Chakraborty, Anirban Chakraborty, Vinod Kumar.

  The host microbiota has emerged as a critical modulator of immunity and cancer pathogenesis, influencing not only tumor initiation and progression but also therapeutic responses. This review explores the multifaceted roles of commensal and engineered bacteria in cancer therapy, highlighting the underlying mechanisms of bacterial tumor targeting, immunomodulation, and synergy with immune checkpoint inhibitors. We summarize the contributions of key bacterial genera-such as Clostridium, Bifidobacterium, Listeria, Salmonella, and Escherichia-focusing on their direct oncolytic properties, delivery systems, and interactions with the tumor microenvironment. Clinical trials employing live bacteria, bacterial metabolites, and fecal microbiota transplantation are also discussed, emphasizing their translational potential and current limitations. Additionally, we explore how the microbiome has been recognized as an enabling hallmark of cancer, capable of influencing inflammation, immune evasion, and therapeutic resistance. Despite significant progress, challenges such as safety, delivery specificity, and regulatory concerns remain. Advances in synthetic biology, precision microbiome engineering, and personalized medicine offer promising strategies to overcome these barriers. By integrating microbial biology with immuno-oncology, bacteria-mediated cancer therapy (BMCT) represents a novel frontier with transformative potential in cancer treatment.

Keywords:  Bacteria; Cancer; Immunotherapy; Microbial metabolites; Oncomicrobiomics; Polymorphic microbiome

DOI:  https://doi.org/10.1016/j.biopha.2025.118559
EcoSal Plus. 2025 Sep 16. eesp00032025

The bacteriophage T4 homologous recombination system: mechanism, applications, conservation, and environmental significance.

Scott W Morrical.

  The homologous recombination (HR) system of bacteriophage T4 plays critical, direct roles in the replication and repair of the phage genome. This review covers the classic, UvsX-dependent HR pathway in T4, focusing on recent findings on the mechanisms of central HR proteins UvsX, UvsY, and Gp32, plus the key helicase and nuclease enzymes that affect HR and promote its coupling to T4 recombination-dependent replication and repair processes. The T4 HR pathways are paradigmatic, since they are highly conserved in all orders of viral and cellular life. Therefore, the study of T4 recombination is highly relevant to biomedicine and to environmental microbiology. At the same time, the tractability of the T4 recombination system for biochemical studies has led to the development of novel, isothermal DNA amplification technologies based on the activities of UvsX, UvsY, and Gp32, which are discussed herein. Globally, the recent revolution in metagenomics has demonstrated that T4-like phages, most encoding the genes and proteins of the T4 HR system, are abundant and widespread in the environment, where they play important roles in the dynamics of diverse microbiomes, from the earth's oceans to the animal gut. Accordingly, we discuss the conservation of T4 HR genes in representatives of T4-like jumbo phages and cyanophages. As a paradigm for HR in diverse organisms, as a source of novel technologies, and as a window on the importance of bacteriophages in the environment, the T4 HR system continues to provide new insights and reagents for a better understanding of life on earth.

Keywords:  DNA strand exchange; Mre11-Rad50; RPA; SIBA; SSB; T4; UvsX; UvsY; amplification; bacteriophage; branch migration; cyanophage; filament; giant phage; helicase; homologous pairing; mediator; nuclease; recombinase; recombination; repair; replication; snap-back

DOI:  https://doi.org/10.1128/ecosalplus.esp-0003-2025
Inflamm Bowel Dis. 2025 Sep 12. pii: izaf184. [Epub ahead of print]

Metagenomic Sequencing Reveals Distinct Gut Microbiome Profiles in Therapy-Naïve de Novo Pediatric Inflammatory Bowel Disease.

Eva Vermeer, Femke M Prins, Iwan J Hidding, Jasmijn Z Jagt, Robert de Jonge, Marc A Benninga, Ranko Gacesa, Rinse K Weersma, Nanne K H de Boer, Tim G J de Meij.

   BACKGROUND AND AIMS: Microbiome studies reveal distinct microbial differences in inflammatory bowel disease (IBD), indicating its potential role in pathophysiology and as a noninvasive diagnostic biomarker. This study aims to profile the gut microbiome in children with IBD, compared to both healthy controls (HC) and controls with gastrointestinal symptoms (CGI), and to assess the potential of microbiome profiles as noninvasive diagnostic markers for de novo treatment-naïve pediatric IBD, and as early predictive markers for therapy response.
METHODS: We analyzed baseline fecal samples and clinical data from 103 therapy-naïve children with IBD, 75 CGI, and 356 age and sex matched HC. Metagenomic sequencing was performed, and prediction models assessed diagnostic potential and prediction of induction therapy response at 3 months.
RESULTS: Alpha diversity progressively decreased from HC to CGI (P < .001) and decreased even further in IBD patients (P = .0056). Beta diversity analysis showed significant clustering differences (P < .001, R2 = 0.045). Differential abundance analysis revealed 116 species differing between HC and IBD, and 30 species between CGI and IBD. Prediction models based on microbiome features accurately distinguished IBD from HC (area under the curve [AUC] = 0.96) and from CGI (AUC = 0.71). However, these models were outperformed by clinical features, such as fecal calprotectin. Microbiome-based prediction of response to induction therapy in general showed limited accuracy (AUC = 0.63), as well as for response to nutritional induction therapy (AUC = 0.67).
CONCLUSIONS: We observed profound gut microbiome differences between de novo, therapy-naïve pediatric IBD patients and controls. While microbiome profiles hold promise for improving diagnostic precision, their predictive value for therapy response seems limited.

Keywords:  Crohn’s disease; gut microbiome; pediatric inflammatory bowel disease; shotgun metagenomics; ulcerative colitis

DOI:  https://doi.org/10.1093/ibd/izaf184
APMIS. 2025 Sep;133(9): e70068

Characterization of a Novel Phage HZJ33 and Its Application in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection.

Ruici Lu, Ruilin Wang, Xuefang Ren, Xinwei Liu, Xiaojuan You, Chunxia Wang, Rui Zhu, Yongwei Li.

  Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical global public health challenge. Phages are regarded as promising alternatives to antibiotics. In this study, a novel lytic phage, HZJ33, was isolated from the clinical CRKP strain KP703. Transmission electron microscopy (TEM) revealed that HZJ33 possessed an icosahedral head and podovirus morphotype. HZJ33 achieved optimal infectivity at a multiplicity of infection (MOI) of 0.01, with a latent period of 10 min and a burst size of 4.65 × 104 PFU/cell. It lysed 40% of tested clinical CRKP isolates (12/30). The endotoxin level released from bacterial lysis mediated by phage HZJ33 was well below the established safety threshold and exhibited no detectable cytotoxicity. Whole-genome analysis confirmed the absence of virulence and antibiotic resistance genes. In vitro, HZJ33 suppressed KP703 growth curves within 10 h. In the Galleria mellonella infection model, HZJ33 treatment at an MOI of 100 increased the larval survival rate to 75%, compared to 25% in the infected negative control group (1 × 107 CFU/mL). These findings identify HZJ33 as a lytic phage with a broad host range, high stability, favorable safety, and strong antibacterial activity in vitro and in vivo, supporting its potential for CRKP therapy.

Keywords:   Klebsiella pneumoniae ; Carbapenem‐resistant; galleria mellonella model; phage therapy

DOI:  https://doi.org/10.1111/apm.70068
Npj Imaging. 2025 Sep 16. 3(1): 42

Fungal infections in focus: accelerating non-invasive imaging from preclinical insights to clinical breakthroughs.

Lauren Michiels, Mahrukh Shameem, Eliane Vanhoffelen, Agustin Reséndiz-Sharpe, Simon A Johnston, Nicolas Beziere, Greetje Vande Velde.

Invasive fungal diseases (IFDs) present a growing clinical challenge, underscoring the urgent need for improved diagnostics, therapeutics and mechanistic understanding. This review highlights the key role of innovative imaging techniques across all scales - ranging from whole-body-level diagnostics and therapy monitoring to host-pathogen interactions at cellular resolution in both clinical and preclinical settings. These imaging modalities facilitate translation of preclinical innovations into clinical applications, accelerating research and advancing IFD management.

DOI: https://doi.org/10.1038/s44303-025-00105-y
Int Wound J. 2025 Sep;22(9): e70766

Wound Care Knowledge of Community Pharmacists and Pharmacy Staff: A Cross-Sectional Survey.

Daisy H K Cheung, Carl R Schneider, Jack C Collins, Irene S Um.

  Chronic wounds pose a public health challenge, with community pharmacists increasingly recognised for their potential role in wound care. Since all chronic wounds originate from acute wounds, pharmacists can play a proactive role in preventing chronicity. Assessing pharmacy staff's wound care knowledge is essential as initiatives to enhance their involvement are underway in Australia. This study aimed to assess wound care knowledge among pharmacists and non-pharmacist staff in Australian community pharmacies. A national cross-sectional electronic survey was conducted between January and August 2022. Developed with multidisciplinary experts, it assessed understanding of wound healing, referral protocols, wound identification, management, and dressing selection. Descriptive and content analyses were performed, and multivariate linear regression identified predictors of knowledge scores. Of 120 responses, 70% were pharmacists, 14% non-pharmacist staff, and 16% unspecified. The median knowledge score was 27 out of 37 (IQR = 21, 30; range = 5-37). Profession, experience, and prior training were significant predictors of higher scores (p < 0.001, R2 = 0.347). Dressing knowledge was weakest, with only 10 out of 103 respondents (9.7%) correctly identifying all types and applications. Critical knowledge gaps underscore the need for targeted educational interventions for pharmacy staff.

Keywords:  community pharmacy services; knowledge; pharmacists; pharmacy technicians; wounds and injuries

DOI:  https://doi.org/10.1111/iwj.70766
Br J Nurs. 2025 Sep 18. 34(17): 877-882

Decolonisation and approaches to this for preventing surgical site infection.

Christopher Gee.

  Surgical site infections (SSIs) are a major cause of postoperative morbidity, financial burden and antimicrobial resistance. Despite evidence-based prevention bundles, adherence varies significantly, with rates of SSIs differing by up to 25-fold between institutions. Decolonisation, particularly nasal decolonisation targeting Staphylococcus aureus, is a critical but underused component of SSI prevention. Options for decolonisation include universal or targeted strategies. National and international guidelines recommend mupirocin as the gold standard, but there are complexities in the screening and administration of the antibiotic as well as potential issues with compliance, time needed to treat and antimicrobial resistance. Alternatives to the use of mupirocin include chlorhexidine, octenidine, povidone-iodine, and a nasal photodisinfection technology. These alternatives may provide practical solutions to some of the challenges associated with antibiotic use but further evidence is required to evaluate their efficacy. Enhanced adherence to decolonisation protocols, supported by robust evidence and aligned with antimicrobial stewardship, offers a clear opportunity to reduce SSIs, improve patient outcomes and support sustainable surgical care. This article explores the current evidence, clinical guidelines and antimicrobial stewardship considerations related to decolonisation strategies.

Keywords:  Antimicrobial resistance; Decolonisation; Nasal photodisinfection; Staphylococcus aureus; Surgical site infection

DOI:  https://doi.org/10.12968/bjon.2025.0368
Eng Life Sci. 2025 Sep;25(9): e70034

Systematic Review on the Role of Microfluidic Platforms in Advancing Scalable and Precise Microbial Bioprocessing.

Alperen Alpural, Ilgin Kimiz-Gebologlu, Mayur Parekh, Esra Imamoglu, Zulfiqur Ali, Ozlem Yesil-Celiktas.

  Microbial bioprocessing is a key technology for the production of a wide range of biomolecules, including proteins, enzymes, antibiotics, and other bioactive compounds. In recent years, there has been an increasing interest in using microfluidic platforms for bioprocessing, due to the ability to precisely control and manipulate fluids at the microscale. Microfluidics offers a transformative platform for the manufacturing of biomolecules intended for clinical applications by addressing key technical challenges in scalability, precision, reproducibility, and the ability to study complex biological systems. In this review, various methods used to fabricate microfluidic platforms and the current state-of-the-art in the synthesis/production of biopharmaceuticals, polymers, bioactive compounds, and real-time monitoring in microscale bioprocesses are discussed. Additionally, the future trends and directions are highlighted. Overall, we envisage the utilization of microfluidic platforms to advance the field of microbial bioprocessing and applications in the biomedical field.

Keywords:  biomedical applications; bioprocess; microfluidics; microreactor; real‐time monitoring; sensors

DOI:  https://doi.org/10.1002/elsc.70034
Ecotoxicol Environ Saf. 2025 Sep 15. pii: S0147-6513(25)01397-1. [Epub ahead of print]303 119052

Phage-based decontamination: Exploring resistance, disinfectant tolerance, and virulence trade-offs in Acinetobacter baumannii.

Yi-Ting Chen, Li-Kuang Chen, Ruei-Sen Jiang, Kai-Chih Chang, Chun-Chieh Tseng.

  Increasing multidrug resistance in Acinetobacter baumannii necessitates a better understanding of how phage resistance influences bacterial fitness, disinfectant tolerance, and virulence. In this study, we induced phage-resistant mutants from the reference strain ATCC 17978 using phages previously applied in clinical decontamination, and we evaluated their physiological adaptations. The wild-type strain initially showed high phage susceptibility but rapidly developed resistance within 24 h. Phage-resistant mutants exhibited changes in plaque morphology and developed at frequencies between 7.6 × 10⁻⁷ and 2.11 × 10⁻⁵. In many cases, these mutants required alternative phages for successful reinfection. Certain phage-resistant strains (e.g., 2R and RB71RR) showed initial fitness reductions (15-20 % fewer generations), which were restored to wild-type levels after 24 h. Whole-genome sequencing of JB68R revealed mutations in glycosyltransferases, IS3 transposases, and peptidoglycan DD-metalloendopeptidases, which correlated with increased ethanol sensitivity (50 %) and enhanced NaDCC tolerance-suggesting potential membrane remodeling as an adaptive mechanism. All phage-resistant mutants exhibited reduced virulence in a Galleria mellonella model, as indicated by lower mortality and melanization responses. To provide a comparative perspective, we also examined colistin-resistant strains generated from ATCC 17978, given the critical role of colistin as a last-line antibiotic. These strains displayed persistent growth impairment (22 % reduced generation number, 32 % lower growth rate; p < 0.01) alongside increased tolerance to hydrogen peroxide (3.3-fold) and benzalkonium chloride (2-fold), indicating a distinct set of resistance trade-offs. These findings underscore the ecological and physiological differences between phage and antibiotic resistance and highlight exploitable vulnerabilities, which could guide the development of more effective, integrated infection control strategies in healthcare settings.

Keywords:  Acinetobacter baumannii; Colistin resistance; Disinfectant susceptibility; Phage resistance; Virulence

DOI:  https://doi.org/10.1016/j.ecoenv.2025.119052
Front Bioeng Biotechnol. 2025 ;13 1646629

Biomaterials strategy for promoting palatal wound healing.

Wen Tong, Junxin Ren, Xinyi Yao, Siyi Wang, Wanhang Li, Liyang Zheng, Xiaoxia Hong, Shufan Zhao.

  Palatal wounds arising from trauma, tumors, cleft palate, or free gingival grafting (FGG) and other etiologies compromise critical orofacial functions including mastication, deglutition phonation and articulation, while posing life-threatening risks in severe conditions. Although surgical resection remains the primary clinical intervention, current treatment strategies for palatal injuries are constrained by several limitations, including: bacterial contamination and chronic inflammation, extensive soft tissue defects, postoperative scar formation, compromised blood supply in the surgical field, and potential patient comorbidities. Research on wound healing based on biomaterials has advanced substantially in recent decades, significantly facilitating their application in tissue engineering. This review provides a comprehensive overview of biomaterials used in palatal wounds, including acellular dermal matrix (ADM), platelet-rich derivatives (e.g., PRF, PRP), amniotic membrane, growth factor, hyaluronic acid, collagen, novel hydrogel, nanofiber scaffolds and other relevant materials. It further discusses potential mechanisms that may be involved in palatal wound healing. The objectives of this review are to summarize recent advances in preclinical and clinical studies on biomaterials for palatal wound healing and to highlight their therapeutic potential in this context.

Keywords:  biomaterials; inflammation; oxidative stress; palatal wound healing; treatment

DOI:  https://doi.org/10.3389/fbioe.2025.1646629
J Biomater Appl. 2025 Sep 18. 8853282251376879

Promotion of infected wound healing by black phosphorus-strontium via photothermal therapy.

Gyeonghwi Yu, Sen Zhang, Jingyi Chen, Guixue Lian, Junhao Zhong, Yongzhe Liu, Xin Xu.

  Bacterial infection, as one of the most common inflammatory complications of skin wounds, presents a critical challenge in clinical treatment: how to effectively control infection while preventing the emergence of drug-resistant strains. In this study, black phosphorus (BP) nanosheets were prepared using the liquid-phase exfoliation method. Strontium ions (Sr2+) were then loaded onto the BP surface via electrostatic self-assembly technology, forming a composite nanomaterial named Black Phosphorus Strontium (BP-Sr) that exhibits both antibacterial properties and the ability to promote soft tissue growth. Utilizing photothermal therapy (PTT), BP-Sr effectively kills bacteria, reduces inflammatory responses, and promotes soft tissue regeneration. This research provides a novel approach for anti-infection treatment and pro-healing strategies for infected wounds.

Keywords:  antibacterial; black phosphorus strontium; non-invasive treatment; photothermal therapy; soft tissue healing promotion; wound infection

DOI:  https://doi.org/10.1177/08853282251376879
Clin Cosmet Investig Dermatol. 2025 ;18 2229-2242

Resveratrol in Dermatological Therapy: A Critical Review of Mechanisms, Delivery Innovations, and Clinical Frontiers.

Quanrui Cui, Heping Wang.

  The management of complex dermatological disorders, including chronic inflammatory diseases, non-healing wounds, and skin malignancies, often faces significant challenges. These include limited efficacy against chronic or relapsing conditions, the emergence of drug-resistant pathogens, and significant side effects from long-term therapies. This clinical gap highlights the urgent need for novel therapeutic agents. Resveratrol (RES), a natural polyphenol with pleiotropic bioactivities, has emerged as a compelling candidate substantiated by its diverse modulatory effects on cutaneous pathophysiology. This review aims to critically synthesize the evidence for RES's efficacy, dissect its foundational mechanisms, and explore innovations in drug delivery designed to overcome its clinical limitations. This review critically synthesizes evidence of the efficacy of RES in managing challenging dermatological conditions, including chronic wounds, psoriasis, atopic dermatitis, melanoma, acne, and herpes simplex virus infections, by dissecting its foundational antioxidant, anti-inflammatory, and immunomodulatory mechanisms. Its therapeutic action is mediated through critical molecular pathways, notably the activation of SIRT1/AMPK and suppression of NF-κB, which collectively mitigate oxidative stress, normalize cellular proliferation, and recalibrate immune responses. Although systemic bioavailability limitations have historically hindered RES's clinical translation, innovative delivery systems, including nanoparticles, hydrogels, and advanced transdermal formulations, are now revolutionizing its topical application and markedly enhancing its localized efficacy and stability. This review consolidates robust preclinical evidence from animal models demonstrating RES-driven accelerated wound healing, diminished inflammatory markers, and significant tumor suppression while also appraising nascent yet promising clinical trial data that indicate good tolerability and initial efficacy in human subjects. Ultimately, this synthesis crystallizes RES as a versatile and promising therapeutic agent in dermatology, concurrently underscoring the imperative for continued innovation in delivery methodologies and execution of large-scale stringently designed clinical trials to fully unlock its therapeutic potential.

Keywords:  clinical trials; dermatological disorders; drug delivery systems; preclinical studies; resveratrol; therapeutic mechanisms

DOI:  https://doi.org/10.2147/CCID.S543849
Data Brief. 2025 Oct;62 112002

Draft genome sequence and intact prophage characterisation of multidrug-resistant Acinetobacter baumannii isolate ABU3 from a tracheal suction specimen in Thailand.

Montri Yasawong, Parweenuch Santaweesuk, Manassanan Phatcharaharikarn, Thunwarat Songngamsuk, Prapimpun Wongchitrat, Umaporn Yordpratum, Tirasak Pasharawipas, Runtikan Pochairach, Warunya Woradulayapinij.

  Multidrug-resistant Acinetobacter baumannii ABU3 was isolated from a tracheal suction specimen from a 76-year-old female patient in Thailand. The draft genome was sequenced using Illumina NextSeq 550. The genome comprised 95 contigs totaling 3826,273 base pairs with an N50 of 112,717 bp and GC content of 38.89. Digital DNA-DNA hybridisation with A. baumannii ATCC 19606T revealed 80.3 % similarity. MLST assigned the isolate to ST-164, whereas MLST of the core genome showed 99.0 % similarity to cgST-4302. Resistance gene analysis identified bla OXA-23, bla CARB variants, bla ADC-25, and tet(39). Antimicrobial susceptibility testing showed resistance to carbapenems, fluoroquinolones, beta-lactam combinations, extended-spectrum cephalosporins, and penicillins, with sensitivity to aminoglycosides and folate pathway inhibitors. Two intact prophage regions (23.5 and 26.3 kb) were identified containing structural and functional components. Data are available at NCBI under BioProject PRJNA550309.

Keywords:  Acinetobacter baumannii; Bacteriophages; Phage therapy; Prophage; ST-164; blaCARB; blaOXA-23; cgST-4302

DOI:  https://doi.org/10.1016/j.dib.2025.112002