bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–11–30
fifty-four papers selected by
Luca Bolliger, lxBio



  1. Viruses. 2025 Oct 29. pii: 1441. [Epub ahead of print]17(11):
      Acinetobacter baumannii is a critical public health threat, particularly with the rise in multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains that limit treatment options. Phage therapy, which uses bacteriophages to target bacteria, offers a promising alternative. We isolated an XDR strain (Ab125) from a burn wound infection and screened 34 phages, identifying vB_AbaM_3098 as the only effective candidate. However, resistance rapidly emerged, producing a derivative strain (Ab139). Interestingly, Ab139, though resistant to vB_AbaM_3098, became susceptible to six previously inactive phages. While various potential determinants were identified through comparative genomics and proteomics, the mechanism causing phage resistance to vB_AbaM_3098 and simultaneous susceptibility to other phages remains to be elucidated. Among the six new candidates, vB_AbaM_3014 was the most promising. While each phage alone allowed bacterial regrowth, combining vB_AbaM_3098 and vB_AbaM_3014 completely suppressed Ab125 growth. In a Galleria mellonella infection model, this cocktail achieved 90% survival after five days compared to 0% in untreated controls. Notably, the cocktail combined one phage with modest activity and another inactive phage against the parental strain; together, they produced strong bactericidal effects. These findings highlight both the complexity of phage cocktail design and their promise as adjunct therapies against drug-resistant A. baumannii.
    Keywords:  Acinetobacter baumannii; Galleria melonnella; bacteriophage; colistin; phage cocktail; phage resistance; phage therapy; phage–antibiotic synergy
    DOI:  https://doi.org/10.3390/v17111441
  2. Front Cell Infect Microbiol. 2025 ;15 1691215
      Klebsiella pneumoniae (K. pneumoniae) is a central pathogen in both nosocomial and community-acquired infections worldwide, capable of causing pneumonia, urinary tract infections (UTIs) and bacteremia. In recent years, the spread of multi-drug resistant (MDR) bacterial pathogens has become a major public health challenge. Traditional antibiotics, which are increasingly ineffective due to escalating resistance, significant adverse effects, and limited therapeutic efficacy, underscore the urgent need for novel strategies. The primary antimicrobial resistance mechanisms of K. pneumoniae currently include alterations of drug target sites, modified enzyme-mediated antibiotic inactivation, permeability barriers to antimicrobial agents, active efflux systems, synergistic resistance mechanisms involving biofilm-persisters-quorum sensing (QS) and heteroresistance. While phage therapy offers precise targeting of pathogenic bacteria, its standalone use is hampered by obstacles such as the rapid evolution of bacterial resistance and narrow host ranges. Accordingly, combinatorial phage therapy has emerged as a key research focus. In this review, we not only summarize the multidimensional antimicrobial resistance mechanisms of K. pneumoniae and the principles of synergistic phage strategies but also evaluate the potential for clinical translation and current challenges, providing a theoretical framework for the precise treatment of multidrug-resistant K. pneumoniae (MDRKP) infections, so as to promote the clinical application of phage-based combination therapy in the post-antibiotic era. Beyond summarizing recent advances, this work also provides a unique translational perspective by critically evaluating the synergy, clinical applicability, and challenges of combinatorial phage approaches-including phage-antibiotic, phage-AMP, and phage-nanocarrier therapies-against MDRKP, filling a critical gap in existing reviews.
    Keywords:  K.pneumoniae; antimicrobial resistance mechanisms; clinical translation; phage; phage-based combination therapy
    DOI:  https://doi.org/10.3389/fcimb.2025.1691215
  3. Antibiotics (Basel). 2025 Nov 14. pii: 1153. [Epub ahead of print]14(11):
      Background/Objectives:Klebsiella pneumoniae is a clinically important pathogen that causes respiratory tract infections, pneumonia, wound infections, urinary tract infections, and sepsis. It is on the World Health Organization (WHO) priority pathogen list as it causes antimicrobial-resistant infections. The aim of this study was to isolate bacteriophages against pan-resistant K. pneumoniae isolated from clinical wound infections. Results: One of the isolated phages, CTF-1, possesses a linear double-stranded DNA genome that is 40,841 base pairs (bp) long and contains 44 predicted genes. Functional assignments were made for 31 of the predicted gene products, which are associated with genome replication, phage packaging, structural proteins, and host lysis, leaving 13 annotated as hypothetical proteins. Based on sequencing analysis, phage CTF-1 is a new member of the genus Przondovirus within the order Autographivirales. Phage CTF-1 was effective against 22 of 25 (88%) pan-resistant K. pneumoniae isolates. The latent period and lytic cycle of the phage were approximately 40 min, with a burst size of about 92 PFU/mL. Conclusions: Our findings suggest that Klebsiella phage CTF-1 is an excellent candidate for phage therapy due to its high lytic activity against pan-resistant K. pneumoniae strains and lack of genes encoding antibiotic resistance, toxins, virulence factors, or integrases.
    Keywords:  Klebsiella pneumoniae; antimicrobial resistance; phage therapy; whole-genome sequencing; wound infection
    DOI:  https://doi.org/10.3390/antibiotics14111153
  4. Antibiotics (Basel). 2025 Oct 27. pii: 1080. [Epub ahead of print]14(11):
      Bacteriophages or phages are viruses that exclusively target and replicate within bacteria, acting as natural predators in the biosphere. Since their discovery over a century ago, host-specific bacteriophages have been widely advocated as a cost-effective and adaptable approach to controlling and combating bacterial infections. Antibiotic resistance, a growing concern and a significant global public health problem, has further underscored the importance of bacteriophages. Nevertheless, their potential applications span diverse fields, including molecular biology, phage therapy, bacterial detection, food safety, and wastewater decontamination. Furthermore, bacteriophages represent a diverse group of viruses that are relatively easy to handle, making them suitable for use in both treatments and biotechnology research. In this review, we aim to provide a comprehensive overview of bacteriophage history, characteristics, and applications that have been employed to address human challenges, ranging from healthcare to environmental remediation. We will highlight key findings and outcomes, shedding light on ongoing research that will shape the future of bacteriophage applications.
    Keywords:  antimicrobial resistance; bacteriophages; environmental remediation; food safety; health therapy; water treatment
    DOI:  https://doi.org/10.3390/antibiotics14111080
  5. Biomed Pharmacother. 2025 Nov 25. pii: S0753-3322(25)00696-1. [Epub ahead of print]193 118502
      In recent years, due to the widespread use of antibiotics, even abuse, the problem of bacterial resistance is becoming more and more serious. Finding new antimicrobial agents and therapeutic methods has become a difficult problem that needs to be solved. Bacteriophages are a general term for viruses that can infect bacteria, fungi, spirochete and other microorganisms. Some bacteriophages can bind specifically to host bacteria, reproduce in the host bacteria and kill the bacteria, and can be used as natural antibacterial agents, which is considered to have the potential to treat multi-drug resistant bacterial infections. This paper introduces the interaction between phage and host, and systematically summarizes the research on bacteriophage in antimicrobial therapy, including the common forms of bacteriophage antibacterial preparations and drug delivery routes, especially the application of bacteriophage as antibacterial agents. Finally, we introduce the application prospect and challenge of bacteriophages in antimicrobial therapy.
    Keywords:  Antibiotics; Antimicrobial treatment; Bacterial infection; Bacteriophages; Phage therapy
    DOI:  https://doi.org/10.1016/j.biopha.2025.118502
  6. Antibiotics (Basel). 2025 Nov 08. pii: 1134. [Epub ahead of print]14(11):
      The global spread of carbapenem-resistant Acinetobacter baumannii (CRAB) poses a severe public health threat, driving growing interest in phage-based precision antibacterial strategies. This systematic review synthesizes recent advances in the field of A. baumannii phage. Modern taxonomy, based on whole-genome phylogeny, has reclassified the majority of A. baumannii phages into the class Caudoviricetes, revealing distinct evolutionary clades that correlate with host tropism and biological properties, superseding the traditional morphological families (Myoviridae, Siphoviridae, Podoviridae). To overcome limitations of natural phage therapy, such as narrow host range, cocktail therapies (ex vivo resistance mutation rates < 5%) and phage-antibiotic synergism (enabling antibiotic efficacy at 1/4 minimum inhibitory concentration) have significantly enhanced antibacterial efficacy. Preclinical models demonstrate that phage therapy efficiently clears pathogens in pneumonia models and promotes the healing of burn wounds and diabetic ulcers via immunomodulatory mechanisms. Technical optimizations include nebulized inhalation delivery achieving 42% alveolar deposition, and thermosensitive hydrogels enabling sustained release over 72 h. Genetic engineering approaches, such as host range expansion through tail fiber recombination and CRISPR/Cas-mediated elimination of lysogeny, show promise. However, the genetic stability of engineered phages requires further validation. Current challenges remain, including limited host spectrum, the absence of clinical translation standards, and lagging regulatory frameworks. Future efforts must integrate metagenomic mining and synthetic biology strategies to establish a precision medicine framework encompassing resistance monitoring and personalized phage formulation, offering innovative solutions against CRAB infections.
    Keywords:  CRAB infection; antibiotic resistance; bacteriophage classification; genetic engineering; phage cocktail therapies
    DOI:  https://doi.org/10.3390/antibiotics14111134
  7. bioRxiv. 2025 Oct 06. pii: 2025.10.06.680661. [Epub ahead of print]
      Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), affect millions annually. UPEC gains access to the urinary tract through mucosal reservoirs including the vaginal tract. With rising antibiotic resistance and frequent recurrence, alternative non-antibiotic strategies like bacteriophage (phage) therapy are gaining attention. We explored the potential of a lytic phage, ΦHP3, as well as a phage cocktail to decolonize UPEC from the urogenital tract using in vitro and in vivo models. Phage significantly inhibited UPEC growth in both bacteriologic medium and simulated vaginal fluid. Pretreatment of human vaginal epithelial cells (VK2/E6E7) and bladder carcinoma cells (HTB-9) with phage reduced adhesion and invasion of UPEC compared with controls. Phage treatment was further able to reduce intracellular UPEC in VK2 cells. Notably, phage pretreatment did not impact phage resistant UPEC strains, indicating that phage lysis was the primary driver of phenotypes. Live confocal microscopy confirmed interaction of phage particles with UPEC and with both epithelial cell lines. In vivo , daily intravaginal ΦHP3 administration in humanized microbiota mice significantly reduced vaginal UPEC burden after 4 days. Treatment with a phage cocktail also reduced vaginal and cervical tissue burdens by day 7 post-treatment. UPEC dissemination was observed to uterine and kidney tissues, but burdens were not different between phage and mock-treated groups. In conclusion, we demonstrate that phage and phage cocktails can modestly reduce UPEC urogenital colonization, highlighting the potential of phage therapy as a viable treatment option for UTI prevention.
    IMPORTANCE: Urinary tract infections (UTIs) are among the most common infections worldwide, with millions of cases each year. Due to frequent recurrence and increasing antibiotic resistance, UTIs are becoming more difficult to treat, and non-antibiotic prevention options remain limited. The bacteria responsible for UTIs, such as uropathogenic E. coli (UPEC), often colonize other body sites, such as the intestines or vagina, before causing infection. In this study, we investigated whether bacteriophage (phage), viruses that infect bacteria, could reduce UPEC colonization. We found that phage treatment decreased UPEC adherence to vaginal and bladder cell lines, but only modestly reduced UPEC vaginal colonization in a mouse model. These findings suggest that phages may offer a potential strategy for UTI prevention, though further research is needed to optimize their therapeutic use.
    DOI:  https://doi.org/10.1101/2025.10.06.680661
  8. Viruses. 2025 Nov 09. pii: 1487. [Epub ahead of print]17(11):
      Phage therapy has garnered significant attention due to the rise of life-threatening multidrug-resistant pathogenic bacteria and the growing awareness of the transfer of resistance genes between pathogens. Considering this, phage therapy applications are being extended to target plant pathogenic bacteria, such as Erwinia amylovora, which causes fire blight in apple and pear orchards. Understanding the mechanisms involved in phage resistance is crucial for enhancing the effectiveness of phage therapy. Despite the challenges of naturally developing a bacteriophage-insensitive mutant (BIM) of E. amylovora (without traditional mutagenesis methods), this study successfully created a BIM against the podovirus ϕEa46-1-A1. The parent strain, E. amylovora D7, and the BIM B6-2 were extensively compared at genomic, transcriptomic, and phenotypic levels. The phenotypic comparison included the metabolic behavior, biofilm formation, and in planta evaluations of pathogenicity. The results revealed a mutation in strain B6-2 in the rcsB gene, which encodes a second regulator in the Rcs two-component phosphorelay system (TCS). This mutation resulted in significant changes in the B6-2 BIM, including downregulation of amylovoran gene expression (e.g., an average log2 fold change of -4.35 across amsA-L), visible alterations in biofilm formation, increased sensitivity to antibiotics (22.4% more sensitive to streptomycin), and a loss of pathogenicity as assessed in an apple seedling virulence model in comparison to the wildtype strain. The findings presented in this study highlight the critical role of the Rcs phosphorelay system in phage resistance in E. amylovora. Based on these findings, we have proposed a model that explains the effect of the B6-2 rcsB mutation on the Rcs phosphorelay system and its contribution to the development of phage resistance in E. amylovora.
    Keywords:  bacteriophage resistance; biopesticide; fire blight; lytic phages; phage-carrier system
    DOI:  https://doi.org/10.3390/v17111487
  9. J Virol. 2025 Nov 26. e0094125
      Since multidrug-resistant Vibrio parahaemolyticus (VP), a deadly pathogenic bacterium responsible for acute hepatopancreatic necrosis disease (AHPND), which has increasingly emerged, bacteriophages have been focused on as an alternative therapy against drug-resistant bacterial infections. Here, we identified various distinct vibriophages, as evidenced by host range assays and restriction fragment length polymorphism analysis. Since we aimed to enhance the efficiency of our previously developed vibriophage cocktail, Eric and Ariel (EA), which has been demonstrated to be effective against VPAHPND, each selected phage was combined with the EA cocktail to evaluate the efficiency of formulated cocktails against VPAHPND isolates. The result revealed that supplementation of the EA cocktail with the phage PhiPS02 yielded outstanding outcomes, particularly against the VPAHPND strain KT1001. The enhanced efficacy of this formulated cocktail was further validated in vivo, where it rescued infected shrimp through a significant reduction of bacterial toxins, leading to approximately 75% survival. PhiPS02 is a novel temperate vibriophage and harbors a genome of 34,737 base pairs encoding genes involved in the lysogenic life cycle. Under physiological stresses that induced prophage activation, PhiPS02-lysogenized bacteria exhibited membrane blebbing and produced small membrane vesicles (MVs) with distinct biomolecular constituents. Interestingly, the combination of lysogen-derived MVs with the EA phage cocktail substantially enhanced bacterial suppression, compared to that of MVs from wild-type bacteria, suggesting a synergistic interaction between lysogen-derived MVs and phages. This study highlights the complex interplay among phages and their bacterial hosts, mediated through lysogen-derived MVs, and provides a novel strategy for the application of temperate phages in the management of VPAHPND in aquaculture.
    IMPORTANCE: Since the resurgence of phage therapy as a strategy to combat antibiotic-resistant bacterial infections, the use of combined virulent phages has shown promising therapeutic potential. However, naturally occurring phages are predominantly temperate, restricting their use as therapeutic agents due to concerns regarding their ability in lysogenic conversion. Here, we demonstrate that temperate phages can confer a therapeutic potential by inducing lysogenized bacteria to produce small membrane vesicles (MVs) that synergize with virulent phages in combination to suppress bacterial growth. Since MVs originate from the bacterial outer membrane, they not only retain phage receptors but also carry phage-derived biomolecules influenced by resident prophage. Potentially, they can mediate receptor transfer to phage-resistant strains via cell-MV fusion and improve phage infectivity through the combined action of phages and prophage-derived enzymes. Our findings provide insights into the role of lysogen-derived MVs and offer strategy into a novel strategy for harnessing temperate phages in therapeutic applications.
    Keywords:  AHPND; Vibrio parahaemolyticus; bacteriophage; membrane vesicles; phage cocktail; temperate phages
    DOI:  https://doi.org/10.1128/jvi.00941-25
  10. Pharmaceuticals (Basel). 2025 Nov 07. pii: 1688. [Epub ahead of print]18(11):
      Antimicrobial resistance (AMR) is one of the most critical challenges to global public health in the 21st century, posing a significant threat to healthcare systems and human health due to treatment failure and high mortality. The World Health Organization (WHO) estimates that, without effective interventions, AMR-associated infections could cause 10 million deaths annually and economic losses of up to 100 trillion US dollars by 2050. The rapid spread of drug-resistant strains, especially in hospital and community settings, has significantly reduced the efficacy of traditional antibiotics. With the continuous advancements in relevant research, bacteriophage (Phage) therapy is constantly innovating in the antimicrobial field. The application of frontier technologies, such as phage cocktails and engineered phages, has significantly enhanced the broad spectrum and high efficiency of phage therapy, which is gradually becoming a new generation of tools to replace antibiotics and effectively combat pathogenic bacteria. However, phage therapy is facing several challenges, including phage inactivation by gastric acid, enzymes, ultraviolet light, and mechanical stress, as well as the potential risk of bacterial phage resistance. Advanced encapsulation technologies such as electrospun fibers, liposomes, chitosan nanoparticles, and electrospray provide solutions to these problems by protecting phage activity and enabling controlled release and targeted delivery. This review addresses phage therapeutic studies of Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes, summarizes the recent advances in phage research, and details the current development and applications of encapsulated phage technologies across various delivery modes.
    Keywords:  CRISPR-CAS; delivery; encapsulation; medicine; phage
    DOI:  https://doi.org/10.3390/ph18111688
  11. PLoS Biol. 2025 Nov;23(11): e3003515
      Capsule diversity is a major limiting factor for phage host range in capsulated bacterial hosts. Phage receptor-binding proteins (RBPs) recognize the capsule and initiate infection, making them key players in phage tropism. In this study, we applied an experimental evolution approach to investigate host range adaptation in a diverse 12-phage community interacting with a Klebsiella spp. community containing 39 distinct capsular types. Our findings revealed that generalist phages possessed highly evolvable RBPs, accumulating non-synonymous mutations that modulated their host range. In contrast, specialist phages acquired fewer mutations but remained stable in the community, maintaining their narrow host range. Additionally, recombination between co-infecting closely related phages facilitated rapid host range adaptation through RBP swapping. However, most recombined genes encoded endonucleases or proteins of unknown function, suggesting their potential role in phage survival. This study advances our understanding of phage host range evolution and provides new insights for optimizing phage-based applications.
    DOI:  https://doi.org/10.1371/journal.pbio.3003515
  12. J Oral Microbiol. 2025 ;17(1): 2584952
       Background: The targeted manipulation of the microbiome using bacteriophages represents a novel approach for addressing antibiotic resistance and polymicrobial diseases.
    Objective: To isolate and characterise bacteriophages for key bacteria associated with pathogenic periodontal biofilms.
    Design: Using standard microbiological and bioinformatics techniques, this study isolated and characterized lytic (FNU2 and FNU3) and temperate (FNU4) bacteriophages specific to Fusobacterium nucleatum, a key bacterium in oral biofilms linked to periodontitis and a range of cancers.
    Results: Morphological and genomic analyses revealed distinct features, with FNU2 and FNU3 classified as Latrobevirus and FNU4 as an unclassified Caudoviricetes. Comparative bioinformatic analysis revealed various defence and anti-defence systems in bacterial hosts and bacteriophages, highlighting complex interactions. Functional assays demonstrated the efficacy of these bacteriophages in disrupting single-species F. nucleatum biofilms and dual-species biofilms of F. nucleatum and Porphyromonas gingivalis.
    Conclusion: These findings highlight the potential of F. nucleatum-specific bacteriophages as precise tools for microbiome modulation in chronic diseases such as periodontitis and cancer.
    Keywords:  Fusobacterium nucleatum subsp. polymorphum; Periodontitis; Porphyromonas gingivalis; dysbiosis; phage therapy; prokaryotic defences
    DOI:  https://doi.org/10.1080/20002297.2025.2584952
  13. Viruses. 2025 Nov 19. pii: 1518. [Epub ahead of print]17(11):
      (1) Background: The emergence of multidrug-resistant (MDR) Salmonella enterica poses a major threat to global public health, underscoring the urgent need for alternative therapeutic strategies. Bacteriophages represent a promising alternative due to their high specificity and potent ability to lyse MDR strains. (2) Methods: In this study, we isolated a novel MDR Salmonella Enteritidis-targeting bacteriophage from Lebanese sewage and characterized its host range, thermal and pH stability, and infection dynamics. Whole-genome sequencing was performed using Illumina technology to determine its genetic features and taxonomic classification. (3) Results: the bacteriophage was classified within the genus Jerseyvirus and the class Caudoviricetes with a 43 kb dsDNA genome encoding 66 open reading frames (ORFs). It demonstrated remarkable thermal stability, retaining infectivity after prolonged incubation at 65 °C, and showed a broad host range. The phage formed large, clear plaques, displayed rapid adsorption (>97% within 3 min), a short latent period (20 min), and a burst size of ~32 PFU per cell. Genome analysis revealed no lysogeny, virulence, or resistance genes, confirming its strictly lytic nature and supporting its potential use as a biocontrol agent. (4) Conclusions: These findings identify SA01 as a novel, strictly lytic, and thermally stable bacteriophage with strong potential as a biocontrol agent against multidrug-resistant Salmonella Enteritidis. Its broad host range suggests potential activity also against other Salmonella enterica serovars, supporting its applicability in food safety and biotechnology.
    Keywords:  Salmonella Enteritidis; bacteriophage; biocontrol; food safety; foodborne pathogens; lytic phage; multidrug-resistant bacteria; phage therapy; thermostable
    DOI:  https://doi.org/10.3390/v17111518
  14. Appl Environ Microbiol. 2025 Nov 24. e0189925
      Bacteriophages (phages), the dominant prokaryotic viruses that specifically target bacteria in the human gut microbiome, play a crucial role in maintaining intestinal balance, regulating bacterial populations, and preserving microbial diversity within the gut microbiota. While prophages can enhance bacterial virulence and antibiotic resistance, potentially posing health risks, they also provide beneficial functions, including enhancing host fitness, promoting immune modulation, and contributing to ecosystem resilience, which supports intestinal homeostasis. Human gut microbiota is essential for various physiological functions, including digestion, vitamin synthesis, immune modulation, and protection against pathogens. Dysbiosis, or microbial imbalance, is associated with various disorders such as inflammatory bowel disease, obesity, diabetes, and mental health disorders. Consequently, prophages are important considerations for developing therapies to prevent intestinal diseases. Recently, there has been significant interest in prophage induction in the gut due to its functional impacts on microbial dynamics, gut health, and disease modulation. Prophage induction can be regulated by diet, antibiotics, metabolites, gut health, lifestyle, and intestinal environments. However, compared with lytic phages, prophages remain underexplored, leaving gaps in our understanding of their functions within the gut. Therefore, further research is needed to fully elucidate the complex interactions between phages, prophages, and the gut microbiota, and their effects on health and disease. This knowledge could inform the development of phage-based therapies and improve therapeutic strategies for gut health.
    Keywords:  bacteriophage therapy; dysbiosis; gut microbiota; lysogeny; microbial diversity; prophage
    DOI:  https://doi.org/10.1128/aem.01899-25
  15. J Clin Med. 2025 Nov 17. pii: 8121. [Epub ahead of print]14(22):
      Wound healing is a complex and multistage process that incorporates precise cellular and molecular coordination. The presence of biofilms in chronic wounds adversely affects the wound healing process, as it prolongs the closure of the wound, thus sustaining chronic inflammation. Current data suggest that biofilms are present in almost all chronic wounds, which leads to significant challenges in diagnosis and treatment. Traditional detection methods, such as cultures and light microscopy, often fail to detect biofilms; however, sophisticated molecular and imaging techniques are constrained by their expense and accessibility. Chronic wound management, therefore, has progressed from conventional antimicrobial application to integrated methodologies that incorporate biofilm debridement, antibiofilm dressing, negative pressure wound therapy, and innovative enzyme or nanoparticle interventions. This review highlights the clinical significance of biofilm presence as a barrier in chronic wound healing, assesses diagnostic and therapeutic innovations, and stresses the urgent need to improve patient outcomes.
    Keywords:  biofilm; chronic; diagnostic; healing; microbiome; resistance; therapeutic; wound
    DOI:  https://doi.org/10.3390/jcm14228121
  16. Brief Bioinform. 2025 Nov 01. pii: bbaf626. [Epub ahead of print]26(6):
      Accurate prediction of virus-host interactions is critical for understanding viral ecology and developing applications like phage therapy. However, the growing number of computational tools has created a complex landscape, making direct performance comparison challenging due to inconsistent benchmarks and varying usability. Here, we provide a systematic review and a rigorous benchmark of 27 virus-host prediction tools. We formulate the host prediction task into two primary frameworks-link prediction and multi-class classification-and construct two benchmark datasets to evaluate tool performance in distinct scenarios: a database-centric dataset (RefSeq-VHDB) and a metagenomic discovery dataset (MetaHiC-VHDB). Our results reveal that no single tool is universally optimal. Performance is highly context-dependent, with tools like CHERRY and iPHoP demonstrating robust, broad applicability, while others, such as RaFAH and PHIST, excel in specific contexts. We further identify a critical trade-off between predictive accuracy, prediction rate, and computational cost. This work serves as a practical guide for researchers and establishes a standardized benchmark to drive future innovation in deciphering complex virus-host interactions.
    Keywords:  bacteriophages; host prediction; metagenomics; prophages
    DOI:  https://doi.org/10.1093/bib/bbaf626
  17. J Infect Public Health. 2025 Nov 17. pii: S1876-0341(25)00407-1. [Epub ahead of print]19(2): 103058
      Antibiotic failure has emerged as a critical global health concern, driven by a combination of factors including the stagnation in the discovery of new antibiotics, the widespread emergence of resistance mechanisms among clinical bacterial isolates, and the persistence of recurrent infections caused by tolerant and non-responsive bacterial populations. This review explores contemporary and innovative anti-infective strategies aimed at countering multidrug-resistant (MDR) and persistent bacterial pathogens. Key approaches discussed include the application of antimicrobial peptides, anti-virulence compounds, bacteriophage therapy, and the development of novel therapeutic molecules. Furthermore, this review highlights the strategic repurposing of existing FDA-approved drugs-such as anti-inflammatory, antipsychotic, anti-helminthic, anticancer agents, and statins-as alternative therapeutics. The integration of artificial intelligence in antimicrobial research is also addressed as a promising avenue to accelerate the identification of effective interventions against MDR infections.
    Keywords:  Antimicrobial peptides (AMPs); Antimicrobial resistance (AMR); Artificial intelligence (AI); Bacterial secondary metabolites; Bacteriophage therapy; Drug repurposing; Monoclonal antibodies; Multitargeted drugs, Nanoparticles (NPs); Non-thermal plasma (NTP)
    DOI:  https://doi.org/10.1016/j.jiph.2025.103058
  18. Viruses. 2025 Nov 04. pii: 1474. [Epub ahead of print]17(11):
      Phages play a role in shaping ecosystems by controlling host abundance via cell lysis, driving host evolution via horizontal gene transfer, and promoting nutrient cycling. The genus Bradyrhizobium includes bacteria able to symbiotically nodulate the roots of soybean (Glycine max), providing the plant with a direct source of biologically fixed nitrogen. Optimizing this symbiosis can minimize the use of nitrogen fertilizers and make soybean production more sustainable. Phages targeting Bradyrhizobium may modify their hosts' genotype, alter phenotypic traits such as symbiotic effectiveness, and mediate competition among strains for nodulation sites. Sixteen phages were isolated against B. diazoefficiens strain USDA110 and B. elkanii strains USDA94 and USDA31. Comparative analyses revealed host species-dependent diversity in morphology, host range, and genome composition, leading to the identification of three previously undescribed phage species. Remarkably, all B. elkanii phages shared a siphophage morphology and formed a single species with >97% nucleotide identity, even when isolated from farms separated by up to ~70 km, suggesting genomic stability across geographic scales. In contrast, phages isolated against B. diazoefficiens had a podophage-like morphology, exhibited greater genetic diversity, and divided into two distinct species. Although no phages were recovered against the B. japonicum strains or native Delaware Bradyrhizobium isolates tested, some Delaware Bradyrhizobium isolates showed susceptibility in a host range assay. The phage genomes demonstrated features predicting phenotypes. The phage terminase genes predicted headful packaging which promotes generalized transduction. The B. elkanii phages all carried tmRNA genes capable of rescuing stalled ribosomes, and all but one of the phages isolated against the two host species carried DNA polymerase A indicating greater phage control of genome replication. State-of-the-art structural annotation of a hypothetical gene shared by the B. diazoefficiens phages, having a mean amino acid identity of ~25% and similarity of ~35%, predicted a putative tail fiber function. Together this work expands the limited knowledge available on soybean Bradyrhizobium phage ecology and genomics.
    Keywords:  Bradyrhizobium; bacteriophages; soybean
    DOI:  https://doi.org/10.3390/v17111474
  19. bioRxiv. 2025 Oct 29. pii: 2025.10.07.681051. [Epub ahead of print]
      Antiphage defense systems confer bacteriophage (phage) resistance in bacteria. Renewed interest in phage therapy indicates a need to understand the breadth and molecular mechanisms of antiphage defenses. Traditionally, strategies to identify antiphage defenses lack throughput or are biased toward model bacteria. Herein, we developed a bioinformatic pipeline that uses a serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our informatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage effector domains and prokaryotic Schlafen proteins support phage defense. Our work shows that serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.
    DOI:  https://doi.org/10.1101/2025.10.07.681051
  20. bioRxiv. 2025 Oct 07. pii: 2025.10.06.680108. [Epub ahead of print]
      Phages play a role in shaping ecosystems by controlling host abundance via cell lysis, driving host evolution via horizontal gene transfer, and promoting nutrient cycling. The genus Bradyrhizobium includes bacteria able to symbiotically nodulate the roots of soybean ( Glycine max ), providing the plant with a direct source of biologically fixed nitrogen. Optimizing this symbiosis can minimize the use of nitrogen fertilizers and make soybean production more sustainable. Phages targeting Bradyrhizobium may modify their hosts' genotype, alter phenotypic traits such as symbiotic effectiveness, and mediate competition among strains for nodulation sites. Sixteen phages were isolated against B. elkanii strains USDA94 and USDA31, and B. diazoefficiens strain USDA110. Comparative analyses revealed host species-dependent diversity in morphology, host range, and genome composition, leading to the identification of three previously undescribed phage species. Remarkably, all B. elkanii phages shared a siphophage morphology and formed a single species with >97% nucleotide identity, even when isolated from farms separated by up to ∼70 km, suggesting genomic stability across geographic scales. In contrast, phages isolated against B. diazoefficiens displayed podophage-like morphology, greater genetic diversity, and divided into two distinct species. Although no phages were recovered against B. japonicum strains or native Delaware Bradyrhizobium isolates tested, some Delaware isolates showed susceptibility during the host range assay. The phage genomes demonstrated features predicting phenotypes. Terminase genes predicted headful packaging among the phages which is critical for generalized transduction. The B. elkanii phages all carried tmRNA genes capable of recruiting stalled ribosomes and both phage groups carried DNA polymerase A indicating greater control of phage genome replication. State-of-the-art structural annotation revealed a tail fiber gene within a phage genome having the highest proportion (80.77%) of unknown genes. Together this work expands the limited knowledge available on soybean Bradyrhizobium phage ecology and genomics.
    DOI:  https://doi.org/10.1101/2025.10.06.680108
  21. Int J Antimicrob Agents. 2025 Nov 20. pii: S0924-8579(25)00228-6. [Epub ahead of print] 107673
       BACKGROUND: There has been renewed interest in phages amidst growing antimicrobial resistance. Their potential for intestinal decolonization is interesting due to their specificity, minimal side effects and microbiota preservation. In addition, phage-resistant bacterial mutants that arise during treatment may become more susceptible to antibiotics and less virulent, possibly leading to better clinical outcomes.
    OBJECTIVES: This study's primary objective is to measure the efficacy of phage-based intestinal decolonization of KPC-producing Klebsiella Pneumoniae (KPC-Kp) at 14 days post-treatment, as well as its feasibility, which is defined as >80% achieving at least 7 days of treatment. Secondary objectives will include phage safety at 14 days post-treatment, intestinal KPC-Kp load change over time, characterization of phage-resistant KPC-Kp mutants, microbiome changes, and infection-related outcomes and general clinical outcomes 3 months after the end of treatment.
    METHODS: This feasibility and proof-of-concept study aims to include 15 high-risk patients recruited from a tertiary Hospital in São Paulo who will receive individualized phage combinations for a mean duration of 14 days. Safety data will be reviewed by an independent Safety Monitoring Board. Description of microbiological techniques is provided.
    CONCLUSION: To the best of our knowledge this is the first published protocol that aims to establish a standardized, individualized phage-treatment framework for intestinal decolonization in a high-endemicity setting. It will also explore phage-bacterial interactions and their broader impact on bacterial virulence and susceptibility profiles. It represents a stepping stone towards implementing phage therapy in South America, and bringing knowledge and capacities to the countries most impacted by escalating AMR.
    Keywords:  KPC-producing Klebsiella pneumoniae; Phage therapy; antimicrobial resistance; intestinal decolonization
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107673
  22. bioRxiv. 2025 Nov 02. pii: 2025.11.01.686033. [Epub ahead of print]
      Viruses are key modulators of human gut microbiome composition and function. While metagenomic sequencing has enabled culture-independent discovery of gut bacteriophage diversity, existing genomic catalogues suffer from limited geographic representation, sparse taxonomic classification, and insufficient functional annotation, hindering detailed investigation into phage biology. Here, we present the Unified Human Gastrointestinal Virome (UHGV), a collection of 873,994 viral genomes from globally diverse populations that addresses these limitations. UHGV provides high-quality virome references with extensive host predictions, comprehensive functional annotations, protein structures, a classification framework for comparative analysis, and a web portal to facilitate data access. Using UHGV to profile worldwide metagenomes, we found that host range breadth is strongly associated with phage prevalence. Additionally, we identified diversity-generating retroelements and DNA methyltransferases as key factors enabling phage populations to access diverse hosts, revealing how specific genomic features contribute to global phage distribution patterns. UHGV is available at http://uhgv.jgi.doe.gov.
    DOI:  https://doi.org/10.1101/2025.11.01.686033
  23. Nurs Stand. 2025 Nov 24.
      Wound care is a complex and evolving practice. Despite a growing body of evidence on wound healing processes and wound infection management, misconceptions about wound care remain entrenched in nursing practice. These misconceptions can result in suboptimal patient outcomes and increase the economic burden on healthcare services. This article critically examines five common wound care myths - regarding moisture balance, wound sterility, wound swabbing, slough and dressing products - and provides guidance for nurses to support them to provide evidence-based wound care aligned with contemporary scientific understanding and principles of best practice.
    Keywords:  clinical guidelines; dressings; evidence-based practice; exudate; nursing care; skin; tissue viability; wound care; wound care products; wound healing; wound management
    DOI:  https://doi.org/10.7748/ns.2025.e12521
  24. Am J Transplant. 2025 Nov 21. pii: S1600-6135(25)03114-4. [Epub ahead of print]
      We report a case series of two lung transplant recipients with chronic, multidrug-resistant Mycobacterium abscessus infections unresponsive to conventional antibiotic therapy, who received intravenous bacteriophage treatment for 12 months under compassionate use. Both patients showed clinical improvement and resolution of the radiological opacities. Gene expression in blood samples collected before and 24 hours after initiation of phage therapy was analysed using the NanoString Host Response panel, revealing immune activation, with increased expression of pro-inflammatory genes (CXCL10 and IL8) and decreased expression of immune evasion pathways (ULK1 and AKT1). These exploratory findings provide insight into potential mechanisms by which bacteriophages may modulate host immunity and support bacterial clearance. Overall, the results suggest that long-term bacteriophage therapy may offer a safe and effective adjunct for managing refractory M. abscessus infections in immunocompromised individuals with chest-localized infection.
    Keywords:  Bacteriophage therapy; Immune response; Immunosuppresion; Lung transplant; Multidrug-resistant (MDR) microorganisms; Mycobacterium abscessus
    DOI:  https://doi.org/10.1016/j.ajt.2025.11.008
  25. Annu Rev Genet. 2025 Nov;59(1): 51-68
      Nucleus-forming jumbo bacteriophages display a surprisingly intricate replication cycle inside of bacterial host cells, challenging the long-standing paradigm of prokaryotic simplicity. The phage nucleus encloses phage DNA in a protein shell, strictly uncouples transcription from translation, and facilitates selective protein import and messenger RNA (mRNA) export, serving the same major functions as the eukaryotic nucleus. Infection of host cells by these phages begins with the formation of a transcriptionally active membrane-bound early phage infection vesicle, demonstrating that these phages are capable of constructing subcellular compartments composed of lipids and proteins. Here, we review the current body of literature revealing the complexities of nucleus-forming phages and the history of the major discoveries. Studies of these phages are revealing new insights into basic principles of subcellular organization, viral speciation, and intracellular viral competition.
    Keywords:  EPI vesicle; chimallivirus; early phage infection vesicle; homing endonuclease; mobile genetic element; phage nucleus; phage tubulin; selfish gene; viral competition; viral factory; viral speciation
    DOI:  https://doi.org/10.1146/annurev-genet-111523-102019
  26. Bioengineering (Basel). 2025 Oct 29. pii: 1178. [Epub ahead of print]12(11):
      Chronic wounds (such as diabetic foot ulcers and pressure ulcers) affect millions of patients worldwide. These non-healing wounds pose major clinical challenges due to persistent inflammation, high infection risk, and impaired tissue regeneration, and incur a substantial healthcare burden, with global wound care costs reaching tens of billions of dollars annually. This unmet need has spurred the development of intelligent wound dressings-advanced bioengineered systems that go beyond conventional passive wound coverings by actively monitoring the wound microenvironment and responding dynamically to promote tissue repair. This review comprehensively examines a broad range of smart wound dressing technologies, including pH-sensitive, temperature-responsive, moisture-responsive, pressure-sensing, electroactive, biosensor-integrated, shape-memory, and controlled drug-releasing systems. We also discuss critical challenges in translating these innovations to clinical practice, such as ensuring biocompatibility and long-term stability in the harsh wound environment, manufacturing scalability and cost-effectiveness, patient comfort and adherence, and navigating regulatory hurdles. By emphasizing recent bioengineering advances and clinical potential, we underscore that intelligent wound dressings represent a paradigm shift in chronic wound management-enabling continuous, personalized therapy with the potential to significantly improve healing outcomes, reduce complications, and improve patient quality of life.
    Keywords:  biosensors; chronic wound healing; intelligent wound dressings; stimuli-responsive materials
    DOI:  https://doi.org/10.3390/bioengineering12111178
  27. Wound Repair Regen. 2025 Nov-Dec;33(6):33(6): e70115
      Chronic wound infections pose significant healthcare challenges due to persistent biofilms, antibiotic resistance, and impaired healing pathways. These wounds are characterised by prolonged inflammation, microbial colonisation, and disrupted tissue regeneration, leading to substantial morbidity and healthcare costs. This article reviews current knowledge on chronic wound types, their pathophysiology, and the mechanisms underlying biofilm formation to examine the latest advancements in antimicrobial-based strategies aimed at addressing these challenges. It highlights how diverse materials and technologies have been engineered to improve infection management, enhance tissue regeneration, and overcome the limitations of traditional treatments as well as advances that leverage innovations such as nanotechnology, advanced drug delivery systems, and bioactive components. Furthermore, the review explores how biomaterials can be tailored to interact with the wound microenvironment, mitigating infection risks while accelerating healing. By analysing the strengths and limitations of these emerging strategies, the review provides insights into the future of chronic wound care by integrating infection biology, biofilm dynamics, diagnostic challenges, and biomaterial-based interventions into a unified framework, highlighting the need for interdisciplinary and strategically layered treatment approaches.
    DOI:  https://doi.org/10.1111/wrr.70115
  28. Rev Med Virol. 2025 Nov;35(6): e70080
      The gut virome, an integral but still poorly understood component of the gut microbiota, is emerging as an important player in the pathophysiology of irritable bowel syndrome (IBS). Recent evidence suggests that alterations in virome diversity and phage-bacteria interactions contribute to gut dysbiosis, immune modulation and gut barrier dysfunction in IBS. This review summarises current knowledge on virome alterations in IBS and emphasises the role of bacteriophages in shaping microbial ecology and host responses. Different virome signatures in the different subtypes of IBS highlight the potential of the virome for disease stratification and personalised therapeutic strategies. In addition, we discuss the analytical challenges in virome research and explore novel virome-targeted interventions, including phage therapy and dietary modulation. A deeper understanding of virome dynamics in the gut could open new avenues for precision medicine approaches to treat IBS.
    Keywords:  bacteriophages; dysbiosis; gut microbiota; gut virome; irritable bowel syndrome; phage therapy
    DOI:  https://doi.org/10.1002/rmv.70080
  29. Antibiotics (Basel). 2025 Oct 22. pii: 1056. [Epub ahead of print]14(11):
      Objectives: To explore the genetic basis of phage resistance in sequentially generated capsular mutants of phage-resistant Klebsiella pneumoniae using an established phage library. Methods: Sequential induction strategies were employed to obtain phage-resistant K. pneumoniae capsular mutants by exposing ST11-K64 K. pneumoniae Kp2325 to different single phages. Whole genome sequencing and bioinformatic analysis were used to elucidate the capsular-related genetic changes in phage-resistant mutants. Phenotypic changes were assessed through gene complementation, growth assays, phage cleavage spectrum analysis, TEM for phage morphology, CPS analysis, biofilm formation, and virulence assays. Results: Three sequentially generated phage-resistant K. pneumoniae capsular mutants were obtained, designated R1, R2 and R3. The narrowing of the phage cleavage spectrum and the evolutionary trade-offs of biological phenotypes were observed. Key genetic changes included: (1) ISKpn26 insertion disrupting wcaJ in R1; (2) combined wcaJ insertion and 9-bp deletion in waaH in R2; and (3) CPS gene cluster deletion in R3 were identified as key mechanisms of phage resistance in K. pneumoniae mutants R1, R2 and R3, respectively. Conclusions: Sequential exposure to different single phages led to rapid evolution of phage resistance in K. pneumoniae via genetic mutations that disrupt capsular synthesis. These findings highlight the critical role of bacterial capsule in phage-host interactions and emphasize the need to use phage cocktails targeting different types of receptors to counteract the evolution of bacterial defense mechanisms in phage therapy.
    Keywords:  Klebsiella pneumonia; capsular polysaccharides; evolutionary trade-off; phage resistance; phage therapy
    DOI:  https://doi.org/10.3390/antibiotics14111056
  30. Virol J. 2025 Nov 25. 22(1): 386
       BACKGROUND: Amidst rising antimicrobial resistance, bacteriophage (phage) therapy has re-emerged as a pivotal weapon against multidrug-resistant pathogens. Jumbo phages, distinguished by large genomes, show particular therapeutic promise. Yet current understanding of jumbo phages is still lacking.
    METHODS: Phage was isolated from domestic sewage. The biological properties of JP4 was characterized via transmission electron microscopy, stability tests, one-step growth curve. The genome of JP4 were elucidated by sequencing and bioinformatics tools. Structural proteins were identified via mass spectrometry. Bactericidal and biofilm eradication activities were evaluated using bacterial turbidity measurements and crystal violet assays, respectively. Statistical significance was determined by using one-way ANOVA in GraphPad Prism.
    RESULTS: Phage JP4 has an icosahedral head (approximately 110 nm in diameter) and a contractile tail (about 120 nm in length). JP4 possesses a linear dsDNA genome of 370,741 bp, encoding 738 proteins and 8 tRNAs. Phylogenetic analysis revealed that JP4 is a new member of the Asteriusvirus genus, and shares close evolutionary relationships with Escherichia phage UB. Additionally, mass spectrometry identified four novel structural protein encoding genes of JP4. Phage JP4 exhibited rapid infection cycle, high stability, potent in vitro bactericidal activity, and strong inhibitory effect on E. coli biofilms.
    CONCLUSIONS: Phage JP4 is a new member of the Asteriusvirus genus. As a lytic jumbo phage with rapid bactericidal activity and strong biofilm degradation capacity, JP4 is a promising therapeutic candidate against E. coli O157:H7 infections. This study provides insights into the diversity and clinical potential of jumbo phages in combating pathogens.
    Keywords:   Escherichia coli ; Antibacterial potential; Biological identification; Genomic analysis; Jumbo phage
    DOI:  https://doi.org/10.1186/s12985-025-03001-4
  31. Pathogens. 2025 Oct 29. pii: 1102. [Epub ahead of print]14(11):
      Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA's antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for periprosthetic joint infection caused by methicillin-resistant Staphylococcus aureus (MRSA-PJI) are limited by considerable side effects, such as high costs and the development of resistance. Therefore, there is an urgent need to explore novel alternative or adjunctive therapies. This review provides a comprehensive overview of several innovative therapeutic strategies. These include monoclonal antibody therapies that target specific bacterial components; phage therapy, which can either independently or synergistically degrade biofilms and enhance antimicrobial efficacy, characterized by its high specificity; antimicrobial peptides, capable of disrupting bacterial membrane integrity and exhibiting dual antibiofilm activity, with a reduced tendency to induce resistance; and nanoparticles and hydrogels, which function as drug delivery systems for sustained release, thereby improving both preventive and therapeutic outcomes. However, these novel therapies also face challenges such as high production costs and limited stability, underscoring the need for further research and optimization. Future efforts should focus on additional studies, clinical trials, and the development of robust regulatory frameworks to fully realize the potential of these treatments for MRSA-PJI.
    Keywords:  enhanced therapy; methicillin-resistant Staphylococcus aureus; new therapy; prosthetic joint infection
    DOI:  https://doi.org/10.3390/pathogens14111102
  32. Int Wound J. 2025 Dec;22(12): e70791
      The number of patients requiring wound care is increasing, placing a burden on healthcare institutions and clinicians. While negative pressure wound therapy (NPWT) use has become increasingly common, Middle East-specific wound care guidelines are limited. An in-person meeting was held in Dubai with 15 wound care experts to develop guidelines for NPWT and NPWT with instillation and dwell (NPWTi-d) use for the Middle East. A literature search was performed using PubMed, Science Direct and Cochrane Reviews. Prior to the meeting, panel members reviewed literature and existing guidelines on NPWT and/or NPWTi-d use. A wound management treatment algorithm was created. Patient and wound assessment at presentation and throughout the treatment plan was recommended. Primary closure was recommended for simple wounds, and NPWT use was suggested for complex wounds requiring wound bed preparation. NPWTi-d use was advised when wound cleansing is required, if the patient is unsuitable for surgical debridement, or if surgical debridement is delayed. When NPWTi-d is unavailable, panel members recommended NPWT. Panel members recommended NPWT for wound bed preparation and NPWTi-d when wound cleansing is needed. These recommendations provide general guidance for NPWT and NPWTi-d use and should be updated as more clinical evidence becomes available.
    Keywords:  algorithm; negative pressure wound therapy; patient care management; surgical wounds; wounds
    DOI:  https://doi.org/10.1111/iwj.70791
  33. Int Wound J. 2025 Dec;22(12): e70796
      Chronic diabetic foot ulcers (DFUs) complicated by osteomyelitis remain a major clinical challenge, often requiring aggressive treatments or surgical intervention. Novel non-invasive approaches such as laser and plasma therapy have shown promise in enhancing wound healing and reducing infection. As part of a broader study involving 20 patients with chronic DFUs (14 females and 6 males), a dual-modality treatment combining low-level laser therapy and PRP therapy was applied. Among the participants, two representative cases are presented in detail to highlight the clinical outcomes and treatment potential of this method. The first case involves a 65-year-old male with a chronic heel ulcer unresponsive to conventional therapies. The second case is a 58-year-old female with a necrotic toe and persistent ulceration. Treatment consisted of multiple sessions of laser and plasma therapy, integrated with standard wound care protocols. Progress was monitored through wound size, tissue regeneration, infection control, and overall healing response. Both patients demonstrated substantial clinical improvement, including resolution of necrotic tissue, reduction in wound size, and formation of healthy granulation tissue. No adverse effects were observed, and neither patient required surgical amputation. Further controlled studies are recommended to validate and generalise these findings.
    Keywords:  PRP therapy; diabetic foot ulcer; low‐level laser therapy
    DOI:  https://doi.org/10.1111/iwj.70796
  34. Bioorg Med Chem. 2025 Nov 23. pii: S0968-0896(25)00437-7. [Epub ahead of print]133 118496
      The rise of antimicrobial resistance (AMR) has outpaced the development of new antibiotics, necessitating alternative therapeutic strategies that do not rely on conventional bactericidal approaches. Quorum-sensing (QS), a bacterial communication system that regulates virulence, biofilm formation and genetic competence, has emerged as a promising non-lethal target. Peptide-based quorum-sensing inhibitors (QSIs) including antimicrobial peptides (AMPs), cyclic dipeptides, and synthetic analogs are gaining recognition for their ability to disrupt QS pathways and attenuate pathogenicity without promoting resistance. This review summarizes recent advancements in peptide-mediated QS interference, covering mechanistic insights, molecular design strategies, and application domains. Natural AMPs such as LL-37 and GH12 modulate QS by altering gene expression or blocking receptor function, while marine-derived cyclic dipeptides act as competitive inhibitors of QS receptors like LasR and CviR. Engineered peptides and peptide-nanocomposite systems have demonstrated improved stability and target specificity, particularly against multidrug-resistant pathogens. Applications span wound healing, prevention of dental biofilms, and prevention of infectious diseases development. However, challenges remain, including peptide instability, low bioavailability, off-target effects, and potential resistance development. Peptide-based QSIs represent a paradigm shift in antimicrobial therapy by disabling bacterial virulence without directly killing cells. Advances in peptide engineering, delivery systems, and synthetic biology are accelerating their clinical and environmental translation. With continued innovation and adapted regulatory frameworks, peptide-based QS inhibition may become a cornerstone of next-generation anti-virulence therapeutics.
    Keywords:  Antimicrobial peptides; Biofilm disruption; Multidrug-resistant pathogens; Peptide therapeutics; Quorum sensing inhibition
    DOI:  https://doi.org/10.1016/j.bmc.2025.118496
  35. bioRxiv. 2025 Oct 24. pii: 2025.10.24.684376. [Epub ahead of print]
      Caulobacter species are Alphaproteobacteria that commonly inhabit plant-associated and aquatic microbial communities. Although Caulobacter is widespread and has long served as a model for the study of bacterial cell biology, our understanding of the diversity of viruses that infect Caulobacter species is limited. Here, we describe the discovery and characterization of Circe, a freshwater N4-like podophage belonging to the Schitoviridae family that infects C. crescentus . We isolated two variants, CirceC and CirceH, that differ by a single nucleotide resulting in an F91I substitution in Gp063, an uncharacterized protein found in diverse bacteriophages and bacteria. While both Circe variants adsorb to C. crescentus with similar efficiency, they produce morphologically distinct plaques and display different infection dynamics. Through forward genetic selection and genome-wide transposon fitness profiling, we identified C. crescentus genes involved in cell envelope assembly, membrane sphingolipid biosynthesis, and envelope polysaccharide biosynthesis that influence susceptibility to Circe infection. Loss-of-function mutations in a predicted nucleoside diphosphate sugar epimerase and multiple genes required for smooth lipopolysaccharide (S-LPS) biosynthesis and export conferred strong resistance to infection. These results support a model in which S-LPS functions as a receptor for phage Circe. Our study expands the known repertoire of Caulobacter phages and adds to a growing understanding of the role of envelope polysaccharides in bacterial infection by N4-family phages.
    IMPORTANCE: Viruses that infect bacteria and archaea, known as phages, shape microbial community structure and function. Phages initiate infection by binding to specific molecules on the surface of host cells. Yet for many microbes, the identities of infecting phages and their corresponding host receptors remain poorly defined. Caulobacter spp. are ecologically important bacteria that can produce a variety of protein surface structures, including pili, a flagellum, and a surface layer (S-layer), all of which have been identified as phage receptors in this genus. We discovered Caulobacter phage Circe and provide evidence that it relies on host smooth lipopolysaccharide to infect C. crescentus . This study broadens understanding of phage-host interactions in Caulobacter and establishes Circe as a new system to investigate the molecular mechanisms by which phages engage with bacterial cells.
    DOI:  https://doi.org/10.1101/2025.10.24.684376
  36. J Oral Biol Craniofac Res. 2025 Nov-Dec;15(6):15(6): 1838-1842
       Background: Periodontitis is a chronic inflammatory disease initiated by polymicrobial infection, characterized by an imbalance between subgingival microbiota and host immune defense. This imbalance results in the destruction of tooth-supporting tissues, with Porphyromonas gingivalis identified as a key pathogen. Conventional periodontal therapies may not fully control destructive inflammation, highlighting the need for effective adjunctive strategies.
    Objective: To evaluate the impact of the probiotic Lactobacillus rhamnosus on inflammatory responses and wound healing processes in an in vivo periodontitis model.
    Methods: Gingival tissue samples from a P. gingivalis-induced periodontitis model were analyzed to determine the effects of L. rhamnosus supplementation on the levels of pro- and anti-inflammatory mediators and wound healing markers.
    Results: In a rat model of periodontitis, probiotic supplementation suppressed inflammation by reducing TNF-α, IL-6, and IL-1β levels while increasing IL-10 expression in the gingival epithelium, thereby restoring the balance between pro- and anti-inflammatory mediators. Additionally, treatment accelerated wound healing, as indicated by upregulation of TGF-β1 and downregulation of MMP-8.
    Conclusion: Our study shows that L. rhamnosus attenuates periodontitis primarily by modulating the host inflammatory response through downregulation of pro-inflammatory cytokines. These findings highlight its potential as an immunomodulatory probiotic and support future clinical trials as an adjunct to conventional periodontal therapy.
    Keywords:  EMT; Inflammation; Periodontitis; Probiotic; Wound healing
    DOI:  https://doi.org/10.1016/j.jobcr.2025.10.025
  37. Microorganisms. 2025 Oct 31. pii: 2516. [Epub ahead of print]13(11):
      The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment.
    Keywords:  asthma; chronic inflammation; dysbiosis; gut microbiome; immune response; inflammatory bowel disease; pathogenesis; psoriasis; rheumatoid arthritis; systemic lupus erythematosus; vasculitis
    DOI:  https://doi.org/10.3390/microorganisms13112516
  38. Pathogens. 2025 Nov 14. pii: 1165. [Epub ahead of print]14(11):
      Acinetobacter baumanni (A. baumannii) is a well-known pathogen associated with antimicrobial-resistant infections. It is a major cause of nosocomial infections and is frequently associated with polymicrobial and antibiotic-resistant infections. This study investigates the frequency of A. baumannii infections, its antimicrobial resistance profile and the main co-pathogens isolated in respiratory samples at the San Giovanni di Dio e Ruggi d'Aragona Hospital in 2015-2019 (pre-COVID-19 pandemic) and 2020-2023 (during/post-COVID-19 pandemic). Bacterial identification and antibiotic susceptibility testing were performed using the VITEK® 2 system (2015-2019), while identification was carried out with MALDI-TOF MS starting from 2020. A total of 1679 strains were isolated between 2015 and 2019, and 1186 between 2020 and 2023, with significantly higher frequencies in males 61-80 and females 71-80. A. baumannii was isolated predominantly from respiratory specimens, derived predominantly in intensive care units (ICUs). The antimicrobial resistance rates of A. baumannii were above 90% for gentamicin, trimethoprim/sulfamethoxazole, imipenem and ciprofloxacin, while colistin resistance was less than 1% (0.95%) in pre-pandemic and alarmingly increased during/post pandemic period (6.1%). A. baumannii was most frequently associated with Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa in respiratory tract infections. A. baumannii represents a serious global health threat due to its extensive antimicrobial resistance, highlighting the need for continuous surveillance, detailed strain characterization, and development of new antimicrobial agents.
    Keywords:  COVID-19; ESKAPE; antimicrobial resistance; nosocomial infections; polymicrobial infections; retrospective study
    DOI:  https://doi.org/10.3390/pathogens14111165
  39. J Microbiol Biotechnol. 2025 Nov 26. 35 e2509050
      Systemic bacteriophage therapy against multidrug-resistant (MDR) Escherichia coli is fundamentally limited by rapid immune-mediated clearance, complement activation, and phagocytic sequestration, collectively constituting pharmacological barriers that restrict systemic bioavailability, shorten circulation half-life, and attenuate therapeutic efficacy. We hypothesized that PEGylation, by sterically shielding phage capsids from host immune clearance mechanisms, would enhance systemic stability, improve pharmacokinetic (PK) behavior, and augment therapeutic efficacy in vivo. Four lytic E. coli phages were covalently conjugated with 5-kDa mPEG-S-NHS, achieving >60% surface amine modification as confirmed by fluorescamine assay. PEGylation resulted in a ~1.5-5 log10 reduction in infectious titer and modestly slowed adsorption kinetics but preserved latent period and burst size, confirming intact replication competence. In serum, wild-type phages were undetectable within 24-48 h, whereas PEGylated phages retained ~2-3 log10 PFU ml-1 at 24 h and persisted longer within RAW264.7 macrophages and HT-29 epithelial cells. In mice, PEGylation markedly increased systemic exposure (AUC0-∞ up to 50-fold), prolonged circulation, and reduced clearance >15-fold. In infected hosts, PEG-EC.W2-6 and PEG-EC. W15-4 achieved plasma titers up to 100-fold higher with >30-fold lower clearance, accelerating bacterial elimination (72 h vs 96 h). Despite partial IgG induction upon repeated dosing, PEGylated phages maintained superior PK and significantly suppressed infection-driven IL-6, IFN-γ, TNF-α, and IL-1β, normalizing cytokine profiles toward baseline. Overall, PEGylation markedly improves systemic persistence, intracellular stability, and immunomodulatory efficacy, representing a robust strategy to overcome PK barriers and optimize systemic phage therapy against MDR E. coli.
    Keywords:  Escherichia coli; In vivo infection model; PEGylation; Phage therapy; multidrug resistance; pharmacokinetics
    DOI:  https://doi.org/10.4014/jmb.2509.09050
  40. J Diabetes. 2025 Dec;17(12): e70173
      The recurrence of diabetic foot ulcers (DFUs) brings significant morbidity to people with diabetes and adds to healthcare costs. According to current guidelines, a DFU is considered healed when it is re-epithelialized, and the wound closure is maintained for around 2 weeks. However, recent literature suggests that the mechanical properties of the underlying plantar tissues remain altered, thus making the foot vulnerable to recurrence. The period lasting several weeks post-DFU healing can be termed the 'transition phase'. This review aimed at exploring this critical phase, with an emphasis on the roles of tissue mechanics and current offloading strategies. An extensive search was performed on PubMed to identify studies on the mechanical properties of the tissues and preventative strategies in the post-healing period. Following the analysis of titles and abstracts, 57 studies met the inclusion criteria and were included in the review. The analysis of the literature revealed that studies are primarily focused on offloading interventions during the remission phase to mitigate long-term ulceration risks. The physiological needs of the still-vulnerable plantar soft tissue after DFU healing are seldom assessed, and no strict differentiation between re-ulceration and recurrent ulceration has been found. According to this review, there is a need for developing beyond state-of-the-art solutions targeting pressure relief and footwear adherence, which consider the varying physiological conditions of the skin and underlying tissue in the transition phase, and the different risk categories and independent risk factors.
    Keywords:  diabetic foot ulcers; footwear; offloading; plantar tissue; recurrence; remission
    DOI:  https://doi.org/10.1111/1753-0407.70173
  41. Colloids Surf B Biointerfaces. 2025 Nov 21. pii: S0927-7765(25)00810-0. [Epub ahead of print]259 115303
      Microneedles (MNs) have emerged as a minimally invasive transdermal platform enabling precise, localized drug delivery with enhanced patient compliance. Coupling MNs with photothermal therapy (PTT) integrates spatially targeted delivery and near infrared-triggered thermal ablation, offering synergistic advantages in tumor treatment, wound healing, and the management of various diseases. This review systematically examines the design strategies of MNs-PTT systems and their applications in different diseases. In tumor therapy, advanced structures and multimodal approaches such as combining PTT with chemotherapy, chemodynamic therapy, immunotherapy and gas therapy, address the limitations of conventional treatments. In wound management, biomimetic architectures and microenvironment-responsive materials enable real-time monitoring and adaptive drug release. For other diseases, including inflammatory skin disorders, ocular diseases, oral diseases, autoimmune conditions, metabolic disorders, and other tissue injuries, MNs-PTT systems provide controlled, on-demand interventions tailored to the specific pathology, thereby improving therapeutic efficacy while reducing side effects. Unlike previous reviews that treat these domains separately, this work provides an integrated cross-domain analysis connecting material and structural innovations to therapeutic performance, thus establishing a unified framework for advancing MNs-PTT systems. Despite these advances, challenges regarding clinical translation still remain. Future progress will rely on interdisciplinary efforts to improve biocompatibility, optimize mechanical performance, and integrate multi-stimuli responsiveness. The combination of AI-assisted design, wearable biosensors, and 3D printing is expected to enhance system precision, safety, and adaptability, accelerating the development of personalized therapies.
    Keywords:  Dermatology; Microneedle; Photothermal therapy; Tumor; Wound
    DOI:  https://doi.org/10.1016/j.colsurfb.2025.115303
  42. Pharmaceutics. 2025 Nov 18. pii: 1486. [Epub ahead of print]17(11):
      Wound healing continues to represent a major clinical challenge worldwide, particularly in the context of chronic wounds, burns, and infection-prone injuries that are increasingly complicated by antimicrobial resistance [...].
    DOI:  https://doi.org/10.3390/pharmaceutics17111486
  43. Expert Rev Clin Pharmacol. 2025 Nov 26. 1-14
       INTRODUCTION: Pediatric chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with multifactorial etiology. CRS is less prevalent in children than in adults, but it substantially affects the patient's quality of life with significant diagnostic and therapeutic challenges.
    AREAS COVERED: This review gives an overview of the pathophysiology, diagnostic approach, and current medical treatment strategies for pediatric CRS.
    EXPERT OPINION: As a first-line medical treatment, standard management includes intranasal corticosteroids and saline irrigation. Short-course antibiotics or systemic corticosteroids are prescribed only when clearly indicated and limited to selected cases. Target therapies as monoclonal antibodies, are considered salvage options for children who do not respond adequately to standard medical or surgical treatments. Dupilumab and tezepelumab are currently the only biologics approved for adolescents with CRS, while other monoclonal antibodies are still under consideration in pediatric CRS. Regulatory approvals are largely based on results extrapolated from adults or from clinical studies conducted in other respiratory diseases. Data on the efficacy and safety of novel therapies are still limited, because pediatric-specific randomized clinical trials are limited. Future studies should focus on the early identification of comorbidities, the development of personalized treatment strategies, and improved safety.
    Keywords:  Pediatric chronic rhinosinusitis; allergen immunotherapy; antibiotics; antihistamine–corticosteroid combination; biologic therapy; intranasal corticosteroids; nasal saline irrigation; oral antihistamines
    DOI:  https://doi.org/10.1080/17512433.2025.2595254
  44. Int J Biol Macromol. 2025 Nov 21. pii: S0141-8130(25)09737-5. [Epub ahead of print]334(Pt 2): 149180
      Advancements in the treatment of antimicrobial infections have highlighted the importance of the CRISPR-Cas system in targeting resistance genes in bacterial pathogens resistant to conventional drugs. Various CRISPR-Cas techniques, such as CRISPR-Cas9, Cas3, dCas9 and the mini-CRISPR system, have been utilized for this purpose in ESKAPE pathogens. Novel strategies like Associates Toxin Antitoxin and CRISPR-Cas to kill multidrug resistant pathogens-CRISPR-regulated toxin antitoxin module (ATTACK-CreTA) and CRISPR interference refine CRISPR-Cas efficacy. This review explores the mechanism of action of resistance genes (e.g., tetM, ermB, VanA, aph-3, aac3, oxa23, blaNDM etc.) prevalent within these pathogens and highlights the notable achievements of CRISPR-Cas technology in targeting these genes, thereby offering a pathway to sensitize resistant bacteria. This article also discusses various delivery approaches for CRISPR components in pathogens, mainly focusing on engineered bacteriophages, including phagemids, temperate phages and virulent phages. Additionally nanoparticles, bacterial conjugation and natural phages hold promise for administering the CRISPR system inside bacteria. Specific targeting of resistance genes in resistant pathogens via CRISPR-Cas based methods would pave a way for combating ESKAPE pathogen infections by reversing the resistance phenotype.
    Keywords:  Antimicrobial resistance; CRISPR-Cas; Engineered bacteriophages; Multidrug resistance; Resistance genes
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.149180
  45. bioRxiv. 2025 Oct 20. pii: 2025.07.03.663053. [Epub ahead of print]
      Since the clinical introduction of antibiotics in the 1940s, antimicrobial resistance (AMR) has become an increasingly dire threat to global public health. Pathogens acquire AMR much faster than we discover new drugs (antibiotics), warranting innovative methods to better understand its molecular underpinnings. Traditional approaches for detecting AMR in novel bacterial strains are time-consuming and labor-intensive. However, advances in sequencing technology offer a plethora of bacterial genome data, and computational approaches like machine learning (ML) provide an optimistic scope for in silico AMR prediction. Here, we introduce a comprehensive multiscale ML approach to predict AMR phenotypes and identify AMR molecular features associated with a single drug or drug family, stratified by time and geographical locations. As a case study, we focus on a subset of the World Health Organization's Bacterial Priority Pathogens, the frequently drug-resistant and nosocomial ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. We started with sequenced genomes with lab-derived AMR phenotypes, constructed pangenomes, clustered gene and protein sequences, and extracted protein domains to generate pangenomic features across molecular scales. To uncover the molecular mechanisms behind drug-/drug class-specific resistance, we trained logistic regression ML models on our datasets. These yielded ranked lists of AMR-associated genes, proteins, and domains. In addition to recapitulating known AMR features, our models identified novel candidates for experimental validation. The models were performant across molecular scales, data types, and drugs while achieving a median normalized Matthews correlation coefficient of 0.89. Prediction performance showed resilience even when evaluated on geographical and temporal holdouts. We also evaluated model generalizability and cross-resistance across the drug-/drug class-specific models cross-tested on other available drug-/drug class genomes. Finally, we uncovered multiple drug class resistance features using multiclass and multilabel models. Our holistic approach promises reliable prediction of existing and developing resistance in newly sequenced pathogen genomes, while pinpointing the mechanistic molecular contributors of AMR. All our models and results are available at our interactive web app, https://jravilab.org/amr .
    DOI:  https://doi.org/10.1101/2025.07.03.663053
  46. Biomedicines. 2025 Nov 20. pii: 2837. [Epub ahead of print]13(11):
      Background/Objectives: Pediatric periodontal inflammation arises from complex host-microbe interactions. Beyond bacterial biofilms, fungal colonization-particularly by Candida albicans-is increasingly recognized as a contributor. The aim of this study was to investigate the relationship between fungal and bacterial colonization, host inflammatory mediators, and salivary parameters in children. It also aimed to identify salivary biomarkers that could be useful for the early diagnosis of oral candidiasis and periodontal inflammation. Methods: A cross-sectional study was performed on 140 children (8-15 years): healthy controls (n = 70) and cases with oral candidiasis (n = 70). Clinical indices (Plaque Index, Gingival Index, Bleeding on Probing), salivary flow, pH, and buffering capacity were recorded. Quantitative PCR assessed C. albicans and four periodontal pathogens, while ELISA measured salivary cytokines (IL-1β, IL-6, TNF-α, IL-8). Analyses included group comparisons, correlations, regression modeling, and principal component analysis (PCA). Results: Children with candidiasis exhibited higher PI, GI, and BOP (p < 0.001), along with reduced pH and buffering capacity (p < 0.001). Salivary loads of C. albicans and all targeted pathogens were elevated (p < 0.001). Cytokine levels were markedly increased (p < 0.001). GI correlated with C. albicans (ρ = 0.71) and cytokines (ρ = 0.62-0.76). Logistic regression identified C. albicans and IL-1β as independent predictors, while salivary pH and flow were found to be protective. PCA distinguished groups, with PC1 (55.2%) driven by fungal and cytokine markers. Conclusions: Oral candidiasis in children is defined by distinct microbial and inflammatory profiles. Salivary biomarker integration offers potential for early, non-invasive diagnosis and risk stratification.
    Keywords:  Candida albicans; cytokines; oral candidiasis; pediatric oral health; periodontal inflammation; salivary biomarkers
    DOI:  https://doi.org/10.3390/biomedicines13112837
  47. Adv Wound Care (New Rochelle). 2025 Nov 26.
      Significance: Wound healing in irradiated skin remains a clinical challenge, with radiation therapy (XRT) resulting in excess collagen deposition and cell death resulting in poor tissue quality. This frequently results in chronic wounds that compromise patient outcomes and quality of life. Recent Advances: Improved understanding of the pathophysiology behind radiation-induced soft tissue injury has led to the development of promising treatments. These include dermal substitutes, placental derivatives, fibronectin, injectable fat-derived and plasma-derived compounds, hyperbaric oxygen, and deferoxamine. Critical Issues: Many traditional approaches to wound healing are often limited by poor tissue quality seen following XRT. A better understanding of mechanisms by which radiation induces these pathological changes may lead to the development of more effective therapeutics. Future Directions: Treatments leveraging recent insights into collateral radiation injury may help to condition tissue to promote healing/regeneration of wounds. Although animal studies and human case reports have been promising, wide-scale clinical studies examining their efficacy are still needed before many of these novel strategies may be adopted to help the millions of patients worldwide suffering from radiation-related cutaneous wounds.
    Keywords:  deferoxamine; ferroptosis; fibronectin; fibrosis; radiation-induced fibrosis; scarring; wound healing
    DOI:  https://doi.org/10.1177/21621918251400347
  48. Curr Diabetes Rev. 2025 Nov 25.
      Diabetic Foot Ulcer (DFU) is a serious and chronic complication of uncontrolled diabetes, significantly increasing the risk of amputation and mortality in diabetic patients. Conventional wound healing techniques often fail to manage chronic wounds in DFU due to several limitations, which eventually raises the need for advanced, innovative, and efficient treatment strategies for the better management of DFU. Many novel interventions, such as growth factor therapy, stem cell therapy, gene therapy, nanotechnology, bioengineered skin substitutes, 3D-bioprinting, and regenerative medicine, have shown promising roles in wound healing and tissue regeneration, suggesting their potential implications in the treatment and control of DFU. An integrated and multidisciplinary approach was proven to be a promising option for rapid and effective DFU management, eventually reducing the financial burden on the patients and healthcare system. Besides, AI-- driven medical technologies were found to support the healthcare system for the prevention, prediction, diagnosis, and personalized treatment of DFU. The present review article provides a brief overview of DFU and its pathophysiology. It highlights traditional DFU treatment strategies, their limitations, and focuses on emerging innovative strategies, emphasizing their potential for addressing DFU. Moreover, it sheds light on challenges and future research areas of these emerging interventions.
    Keywords:  Diabetic foot ulcer; conventional therapies; novel strategies.; pathophysiology; wound healing
    DOI:  https://doi.org/10.2174/0115733998407601251010114114
  49. bioRxiv. 2025 Oct 15. pii: 2025.10.13.682247. [Epub ahead of print]
      Bacteriophages offer advantages over small-molecule antibiotics, including host specificity and general compatibility with the human phagenome. However, their evolvability as replicating biological entities introduces therapeutic unpredictability and risks of phage-bacteria co-evolution. Here, we retain the targeting benefits of phages while avoiding genetic replication by engineering genetic-information-free, protein-only phages (POPs). These genome-free particles self-assemble in a cell-free protein synthesis system from modular, de novo gene fragments encoding only structural and antimicrobial proteins. Using Enterobacteria phage T7 and its susceptible bacterial host as a model, we test the hypothesis that POPs stochastically encapsulate small antimicrobial proteins during self-assembly and deliver them into bacteria during adsorption via an ejectome-mediated injection mechanism. A computational survey of T7 small proteins revealed early and mid-genome enrichments of hypothetical proteins and capsid volume sufficient to accommodate multiple small proteins in the absence of the ∼40-kb genome. In time-series antimicrobial susceptibility assays (48-72 h), POPs produced initial growth inhibition comparable to wild-type T7 at the highest doses with a linear dose-effect relationship and a minimum inhibitory concentration-like threshold. These results establish the feasibility of genetic-information-free POPs as protein-based antimicrobials that couple phage receptor specificity with minimal biosafety risks, supporting the development of more stable and predictable phage-inspired therapeutics.
    DOI:  https://doi.org/10.1101/2025.10.13.682247
  50. Front Immunol. 2025 ;16 1710733
      Dysregulation of the homeostasis between regulatory T cell (Treg) and T helper 17 cell (Th17) is increasingly recognized as a pivotal mechanism in the pathogenesis of autoimmune diseases. Emerging evidence indicates that gut microbiota-derived metabolites, including short-chain fatty acids, secondary bile acids, and aromatic metabolites, modulate Treg/Th17 balance by shaping immune cell differentiation and function, thereby revealing novel therapeutic opportunities. This Review synthesizes recent clinical and preclinical findings on the influence of microbial communities and their metabolites on Treg/Th17 dynamics and examines the underlying mechanisms in representative autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, autoimmune hepatitis, and myasthenia gravis. We critically evaluate current microbiome-targeted interventions and discuss their translational potential, highlighting both promises and challenges. Finally, we outline priorities for future research, focusing on multi-omic integration, the development of individualized therapeutic strategies, and rigorous clinical evaluation, to facilitate the development of safe and effective microbiota-based therapies for autoimmune diseases.
    Keywords:  Treg/Th17 balance; autoimmune diseases; gut microbiota; immune regulation; microbial metabolites; therapeutic targets
    DOI:  https://doi.org/10.3389/fimmu.2025.1710733
  51. Med Arch. 2025 ;79(5): 411-416
       Background: Understanding the aging process has become one of the global concerns as the world faces the new challenges of an aging population. Central to this phenomenon is cellular senescence, marked by an irreversible growth arrest due to cellular damage. Gut microbiome is a dynamic community of microorganisms influenced by diet, environmental exposures, and aging.
    Objective: This research highlights the significant impact of gut microbiota composition on overall health, particularly in older adults, where deterioration in microbial diversity can lead to adverse health outcomes. Kombucha, a fermented tea beverage, has emerged as a potential gut microbiota modulator, offering antioxidant properties and digestive support. Specifically, Kombucha derived from Areca catechu shows promise in modulating inflammatory markers and gut microbiota composition.
    Methods: This review synthesizes current literature on the relationship between aging, frailty, and gut health, with a particular focus on gut microbiota composition and chronic inflammation, referred to as "inflammaging." We specifically investigate the potential of Kombucha, a fermented tea beverage, to modulate gut microbiota and inflammatory markers.
    Results: Kombucha, a fermented tea beverage, has emerged as a potential gut microbiota modulator, offering antioxidant properties and digestive support. Specifically, Kombucha derived from Areca catechu shows promise in modulating inflammatory markers and gut microbiota composition. This review synthesizes current literature on the interplay between aging, frailty, and gut health-focusing on the role of gut microbiota and chronic inflammation ("inflammaging")-to elucidate the therapeutic potential of Kombucha in promoting gut health and mitigating age-related decline, thereby contributing to a deeper understanding of its role in the aging process.
    Discussion: This research elucidates the therapeutic potential of Kombucha in promoting gut health and mitigating age-related decline, contributing to a deeper understanding of its role in the aging process. The interplay between gut microbiota and chronic inflammation highlights the importance of dietary interventions in managing health in aging populations.
    Conclusion: Kombucha presents a viable strategy for modulating gut health and addressing the challenges of aging, emphasizing the need for further exploration of its benefits in older adults.
    Keywords:  Elderly; Inflammatory Marker; Kombucha; Microbiota
    DOI:  https://doi.org/10.5455/medarh.2025.79.411-416
  52. Microorganisms. 2025 Oct 29. pii: 2465. [Epub ahead of print]13(11):
      Fecal microbiota transplantation (FMT) is increasingly used in both human and veterinary settings to restore gut microbiota and promote health. Advances in sequencing technologies and microbiome analysis have expanded our understanding of microbial communities and enabled broader FMT applications. As insights grow into what constitutes a healthy microbiome, interest in using FMT across a range of animal contexts has also increased. This narrative review highlights recent progress in the use of FMT to improve the welfare of farm animals, manage infectious and chronic conditions in companion animals, and support the health of wildlife in conservation and reintroduction programs. Representative examples from each domain are discussed.
    Keywords:  animal health; conservation biology; fecal microbiota transplantation; microbiome; veterinary medicine
    DOI:  https://doi.org/10.3390/microorganisms13112465
  53. Cell Commun Signal. 2025 Nov 24. 23(1): 504
      Skin microbiota emerged as an important factor in modulating all aspects of the wound healing process, with the potential utilization of residing microbes as biological therapeutics. Commensal or probiotic bacteria represent a first layer of the cutaneous barrier protection, inhibiting detrimental effects of pathogens and modulating cutaneous immune response. In this review, we highlight the latest findings on pro-healing ability of a new subclass of probiotic-derived products named postbiotics, defined as preparations of inanimate microorganisms and/or their components that confer a health benefit on the host. By mimicking the beneficial effect of live probiotics, postbiotics have the ability to restore healthy skin microbiome through inhibition of pathogen colonization and biofilm formation. Postbiotics also regulate skin epithelial barrier function and cutaneous immune response to suppress intracellular pathogen invasion. In order to effectively restore barrier breach, postbiotics stimulate multiple cellular components of the cutaneous wound healing process. This review describes molecular and cellular aspects of host-postbiotics interactions during cutaneous wound healing and provides a current viewpoint of therapeutic potential and advantages of postbiotics application for treatment of cutaneous wound healing disorders. In the era of rising antimicrobial resistance and epidemic proportions of wound healing disorders, probiotic-based therapeutics offer safe, effective and yet underutilized solutions for unmet clinical need.
    Keywords:  Chronic wounds; Commensal bacteria; Dysbiosis; Epithelial barrier; Keratinocytes; Postbiotics
    DOI:  https://doi.org/10.1186/s12964-025-02494-4
  54. Nature. 2025 Nov 25.
      
    Keywords:  Diseases; Health care; Microbiology; Microbiome; Research data
    DOI:  https://doi.org/10.1038/d41586-025-03872-1