bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–09–07
nineteen papers selected by
Luca Bolliger, lxBio
  1. Bacteria-phage infection network structure and genomic defence system content predict efficacy of a phage therapy cocktail against Pseudomonas aeruginosa from chronic lung infections.
  2. Why do bacteria accumulate antiphage defence systems?
  3. Phage quest: a beginner's guide to explore viral diversity in the prokaryotic world.
  4. [Clinical efficiency of polyvalent piobacteriophage in the complex treatment of nosocomial sinusitis].
  5. Updated phage banks essential to cope with pathogen evolution: Lessons from Klebsiella pneumoniae and their phages.
  6. Nanocoated bacterial carriers enhance oral bacteriophage delivery efficiency.
  7. Isolation and characterization of bacteriophages from clinical enterohemorrhagic Escherichia coli strains.
  8. Lineage-specific defence systems of pandemic Vibrio cholerae.
  9. The discovery of a Legionella phage explains a key determinant of human disease.
  10. Bacteriophage immunotherapy with artificial antigen-directed immune labeling against bacterial infection.
  11. Antibiotic-resistant Acinetobacter baumannii can be killed by a combination of bacteriophages and complement.
  12. Susceptibility profile of clinical and food-associated Listeria monocytogenes strains to a commercial phage product using different test methods.
  13. Capsid redirection mechanism of the Staphylococcus aureus pathogenicity island SaPIpT1028.
  14. Updates in Clinical Management of Recurrent Urinary Tract Infections.
  15. Colistin resistance in the era of antimicrobial resistance: challenges and strategic countermeasures.
  16. DeepBiome: A Phylogenetic Tree Informed Deep Neural Network for Microbiome Data Analysis.
  17. Rapid and Esthetic Wound Healing in Surgery by Applying a Powdered Mixture of Mannose and Calcium Propionate.
  18. Commercial Bacteriophage Cocktail Treatment Reduces Salmonella Infantis Levels in Pre-Harvest Agricultural Water.
  19. Visualization of multidrug-resistant bacterial infection trends in the intensive care units.
  1. Philos Trans R Soc Lond B Biol Sci. 2025 Sep 04. 380(1934): 20240080
    Bacteria-phage infection network structure and genomic defence system content predict efficacy of a phage therapy cocktail against Pseudomonas aeruginosa from chronic lung infections.
    Maisie R Czernuszka, Taoran Fu, Anastasia Kottara, Michael A Brockhurst, Rosanna C T Wright.
      Pseudomonas aeruginosa chronic lung infections pose serious challenges for phage therapy due to high between-patient strain diversity and rapid within-patient phenotypic and genetic diversification, necessitating simple predictors of efficacy to streamline phage cocktail design. We quantified bacteria-phage infection networks (BPINs) for six phages against 900 P. aeruginosa clones previously isolated from 10 bronchiectasis infections (n = 90 isolates per patient). BPIN structure varied extensively between patients. The efficacy of the six-phage cocktail against these diverse P. aeruginosa populations was influenced by several factors. Cocktail efficacy increased with decreasing number and strength of individual resistances, as well as with increasing co-resistance modularity and phage dose. These results highlight simple BPIN metrics that could help guide the design of effective phage therapeutics. Resistance against some but not all the phages increased with higher number defence systems per genome, resulting in lower efficacy of the six-phage cocktail, suggesting that P. aeruginosa strains with fewer defence systems are better candidates for phage therapy. Overall, our findings suggest that 'off the peg' phage therapeutics are unlikely to be broadly effective against P. aeruginosa chronic respiratory infections, but that the design of personalised phage cocktails could be guided using simple BPIN metrics, and that defence systems per genome provide a useful rule of thumb for identifying highly treatable infections.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
    Keywords:  Pseudomonas aeruginosa; anti-phage defence system; bacteria–phage infection network; chronic infection; phage therapy
    DOI:  https://doi.org/10.1098/rstb.2024.0080
  2. Philos Trans R Soc Lond B Biol Sci. 2025 Sep 04. 380(1934): 20240082
    Why do bacteria accumulate antiphage defence systems?
    Tyler Clabby, Florian Tesson, Baptiste Gaborieau, Aude Bernheim.
      While it is well established that bacterial genomes encode multiple and diverse antiphage systems, the reasons for their co-occurrence and their heterogeneous distribution remain debated. This review examines why bacteria accumulate antiphage systems and how this influences phage-bacteria interactions, particularly in the context of phage therapy. Two main hypotheses may explain this phenomenon: (i) the pan-immunity hypothesis, which suggests that defence system accumulation provides protection against phage predation at the community level, and (ii) mobile genetic element (MGE) competition, where defence systems primarily protect intra-bacterial MGEs against other ones rather than the bacterial host itself. The ecological context also influences the distribution of antiphage systems, with defencee accumulation shaping phage-bacteria interactions in diverse communities but playing a lesser role at the species level, potentially explaining why multiple defences do not strongly limit phage host range in therapeutic settings. Finally, we address the challenges in understanding the drivers shaping the distribution of defence systems across bacterial genomes (expressions, costs, etc.) and their implications for elucidating the ecological role of defence systems and optimizing phage therapy strategies.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
    Keywords:  bacteriophage; defence systems; host range; mobile genetic elements; phage therapy
    DOI:  https://doi.org/10.1098/rstb.2024.0082
  3. Brief Bioinform. 2025 Aug 31. pii: bbaf449. [Epub ahead of print]26(5):
    Phage quest: a beginner's guide to explore viral diversity in the prokaryotic world.
    Carolin Charlotte Wendling, Marie Vasse, Sébastien Wielgoss.
      The increasing interest in finding new viruses within (meta)genomic datasets has fueled the development of computational tools for virus detection and characterization from environmental samples. One key driver is phage therapy, the treatment of drug-resistant bacteria with tailored bacteriophage cocktails. Yet, keeping up with the growing number of automated virus detection and analysis tools has become increasingly difficult. Both phage biologists with limited bioinformatics expertise and bioinformaticians with little background in virus biology will benefit from this guide. It focuses on navigating routine tasks and tools related to (pro)phage detection, gene annotation, taxonomic classification, and other downstream analyses. We give a brief historical overview of how detection methods evolved, starting with early sequence-composition assessments to today's powerful machine-learning and deep learning techniques, including emerging language models capable of mining large, fragmented, and compositionally diverse metagenomic datasets. We also discuss tools specifically aimed at detecting filamentous phages (Inoviridae), a challenge for most phage predictors. Rather than providing an exhaustive list, we emphasize actively maintained and state-of-the-art tools that are accessible via web or command-line interfaces. This guide provides basic concepts and useful details about automated phage analysis for researchers in different biological and medical disciplines, helping them choose and apply appropriate tools for their quest to explore the genetic diversity and biology of the smallest and most abundant replicators on Earth.
    Keywords:  bacteriophages; gene annotation; metagenomics; microbial bioinformatics; phage prediction; prophages
    DOI:  https://doi.org/10.1093/bib/bbaf449
  4. Vestn Otorinolaringol. 2025 ;90(4): 33-38
    [Clinical efficiency of polyvalent piobacteriophage in the complex treatment of nosocomial sinusitis].
    A I Kryukov, A V Gurov, D S Cherkasov, M A Magomedov, A A Lapchenko, Y A Raji, E O Yarushina.
      The article presents the results of the study of polyvalent pyobacteriophage in the complex therapy of nosocomial sinusitis in 30 patients of intensive care units of a multidisciplinary hospital in Moscow. The etiologic factors of nosocomial sinusitis manifestation were the following microorganisms: Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Acinetobacter nosocomialis, Pseudomonas aeruginosa, Proteus mirabilis, Enterobacter aerogenes. According to the results of the study it was revealed that at the empirical phage therapy the regression of the main clinical symptomatology was achieved in 90% of patients. The average number of days of this therapy before registration of clinical sanation of the maxillary sinus was 4±1.9. Microbiological sanitation of the maxillary sinuses was achieved in 46.7% of cases.
    Keywords:  bacteriophages; nosocomial infections; nosocomial strains of microorganisms; phage therapy; sinusitis
    DOI:  https://doi.org/10.17116/otorino20259004133
  5. J Microbiol Immunol Infect. 2025 Aug 29. pii: S1684-1182(25)00178-1. [Epub ahead of print]
    Updated phage banks essential to cope with pathogen evolution: Lessons from Klebsiella pneumoniae and their phages.
    Pallavi Bhat Ajakkala, Apoorva R Kenjar, Sujana Prabell, Sushma Bhandarkar, Shreya Bhat, Akhila Dharnappa Sannejal, Anusha Karunasagar, Ashwini Chauhan, Indrani Karunasagar, Juliet Roshini Mohan Raj.
       BACKGROUND: Multidrug-resistant Klebsiella pneumoniae (MDR-KP) leads global health concerns as an infectious agent due to many virulence factors, including biofilm formation. The growing urgency for alternative treatment strategies beyond antibiotics has renewed interest in bacteriophages. Pathogen evolution is dynamic and can lead to phage resistance.
    METHODS: Bacteriophages were isolated from environmental sources and screened against a panel of 280 MDR- K. pneumoniae clinical isolates (74 from 2018 to 2020 and 167 from 2022-23 and 39 environmental KP isolates). Phages were grouped by host range and DNA fingerprinting. Five candidate phages with unique and broad host coverage were selected for further characterization and genome sequencing.
    RESULTS: Five candidate phages exhibited diverse host range patterns, strong bacteriolytic activity and significant antibiofilm activity even at low multiplicity of infection. Whole genome sequencing analysis revealed phage KPØ6 to be a novel Taipevirus species with low intergenomic similarity to known phages, and it showed the broadest host range on isolates from the 2018-2020 panel. A significant rise in phage resistance among MDR-KP isolate panels of 2018-2020 and 2022-2023 was observed.
    CONCLUSION: Lytic bacteriophages offer a promising alternative for tackling MDR-KP infections, especially within healthcare environments. The phages characterized in this study demonstrate strong potential for both biocontrol and therapeutic use against MDR-KP, including infections involving biofilms. However, the dynamic nature of bacterial evolution over five years reiterates the need to update phage banks.
    Keywords:  Antimicrobial resistance; Bacteriophages; Biofilm; Host range; Whole genome analysis
    DOI:  https://doi.org/10.1016/j.jmii.2025.08.022
  6. Acta Pharm Sin B. 2025 Aug;15(8): 4319-4321
    Nanocoated bacterial carriers enhance oral bacteriophage delivery efficiency.
    Yingui Cao, Aodi Jiang, Qiang Gao, Bo Xiao.
      
    Keywords:  Bacterial carrier; Bacterially induced enteritis and associated arthritis; Phage therapy; Polymer coating
    DOI:  https://doi.org/10.1016/j.apsb.2025.05.037
  7. Microbiol Spectr. 2025 Sep 05. e0059725
    Isolation and characterization of bacteriophages from clinical enterohemorrhagic Escherichia coli strains.
    Jessie Vandierendonck, Adam Valcek, Van Son Nguyen, Didier Vertommen, Surbhi Malhotra-Kumar, Henri De Greve, Remy Loris.
      Temperate bacteriophages play a pivotal role in the biology of their bacterial host. Of particular interest are bacteriophages infecting enterohemorrhagic E. coli (EHEC) due to their significant contribution to the pathogenicity of its host, most notably by encoding the key virulence factor of this pathogen, the Shiga toxin. To better understand the role of EHEC phages on the functionality of its host, we isolated eight temperate phages from clinical EHEC isolates and characterized their genomic composition, morphology, and receptor targeting. Morphological analysis identified one long-tailed siphophage, targeting the OmpC receptor for host recognition, whereas the other seven phages are short-tailed podophages and target the essential BamA protein. Genomic characterization revealed significant variations between the long- and short-tailed phages. Five of the eight isolated phages encode the potent Shiga toxin. Comparative analysis displays the typical lambdoid mosaicism, indicative of horizontal gene transfer driving evolution. These findings provide insights into the genetic and morphologic diversity and receptor specificity of EHEC phages, highlighting their role in the evolution and pathogenicity of clinical EHEC strains.IMPORTANCECharacterizing bacteriophages from clinical EHEC isolates is crucial in understanding the mechanisms underlying bacterial evolution and virulence. Despite the clinical relevance of EHEC bacteriophages, they remain underexplored, and particularly phage receptors are often not characterized. Studying temperate EHEC phages is essential in the development of strategies to address the global burden of these foodborne infections. Notably, identifying the phage receptors is critical in unraveling the specific interaction between phage and host. Knowledge of the phage receptors can provide insights into the mechanisms of phage infection, host range, and bacterial resistance and is fundamental in the design of targeted therapies like new antimicrobials, phage therapy, or prevention of those infections.
    Keywords:  Shiga toxin; bacteriophage receptor; enterohemorrhagic E. coli; genome sequencing; temperate bacteriophages
    DOI:  https://doi.org/10.1128/spectrum.00597-25
  8. Philos Trans R Soc Lond B Biol Sci. 2025 Sep 04. 380(1934): 20240076
    Lineage-specific defence systems of pandemic Vibrio cholerae.
    Melanie Blokesch, Kimberley D Seed.
      Cholera remains a significant global health burden. The causative agent responsible for the ongoing cholera pandemic, which began in 1961, is the seventh pandemic El Tor (7PET) lineage of Vibrio cholerae. Over the past century, lineages of V. cholerae have been traced using phage typing schemes, DNA hybridization on microarrays and, more recently, comparative genomics enabled by next-generation sequencing. Such lineage tracing has provided essential insights into cholera transmission dynamics. Beyond their use as tools in typing schemes, phages have long been recognized as major players in cholera epidemiology. Importantly, the integration of comparative genomics, epidemiology and molecular studies has recently provided compelling evidence that bacterial defence systems, along with the evolutionary adaptations of phages to counteract them, play critical roles in the ongoing arms race between pandemic V. cholerae and their phages, with phage resistance likely influencing cholera epidemiology. In this review, we explore abundant and sporadic defence systems in sub-lineages of 7PET V. cholerae and describe how they protect their bacterial hosts from predatory phages. Additionally, we contrast these findings with the defence activities observed in the sixth pandemic classical lineage of V. cholerae. Finally, we discuss the experimental challenges and limitations associated with studying defence systems in V. cholerae and propose future directions to advance research in this field.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
    Keywords:  bacteriophage; cholera; phage defence
    DOI:  https://doi.org/10.1098/rstb.2024.0076
  9. Sci Adv. 2025 Sep 05. 11(36): eadx9722
    The discovery of a Legionella phage explains a key determinant of human disease.
    Beth Nicholson, José F Santé, Elizabeth H Chaney, Justin C Deme, Shayna R Deecker, Kristina Sztanko, Alan R Davidson, Susan M Lea, Alexander W Ensminger.
      Host cells provide intracellular bacteria with protection from harsh environmental conditions and immune responses, but for many intracellular pathogens, this protection does not appear to be absolute as once thought. Bacteriophages that can kill bacteria inside host cells have been identified for pathogens including Salmonella, Mycobacterium, and Chlamydia species. Even in pathogens for which no stable phages have been isolated, such as Legionella pneumophila, the presence of phage defense systems suggests phage susceptibility. Here, we report the stable isolation of Legionella bacteriophage LME-1 (Legionella mobile element-1) and its impact on bacterial virulence in humans. Cryo-electron microscopy of the capsid (2.1 angstroms) and portal-tail complex (1.9 angstroms) reveals an unambiguous phage particle with T7-like morphology. Characterizing the host range of this phage, we make a serendipitous finding that links the acquisition of a phage defense mechanism to the formation of a virulent clade of L. pneumophila responsible for 80% of all Legionnaires' disease.
    DOI:  https://doi.org/10.1126/sciadv.adx9722
  10. Sci Adv. 2025 Aug 29. 11(35): eadr1911
    Bacteriophage immunotherapy with artificial antigen-directed immune labeling against bacterial infection.
    Minjun Yao, Liang Chen, Xiaoqiang Jin, Zhenxuan Shao, Yucheng Xue, Wenkan Zhang, Hao Zhou, Shenzhi Zhao, Haochen Mou, Shixin Chen, Eloy Yinwang, Jiahao Zhang, Xiaoyong Wu, Kanbin Wang, Chenhe Zhou, Xunzi Cai, Chen Zhuang, Rongxin He, Jianbin Xu, Zhaoming Ye.
      Bacteriophage therapy has been recognized as a promising anti-infection alternative, while its clinical therapeutic outcomes are compromised due to the development of bacterial resistance, ongoing host immune dysfunction at infection sites, and their failure to adequately revitalize host immunity. Here, we present a strategy for artificial antigen-directed immune labeling of bacteria, capitalizing on residual bacteriophage capsids on bacterial surfaces, which enable immune cells to achieve quicker bacterial recognition and clearance. Specifically, Mn2+@Man-phage anchored on bacterial surfaces and provided artificial recognition sites that enabled macrophages to phagocytize via mannose receptors, accompanied by enhanced bactericidal activity triggered by manganese ions in response to an infectious microenvironment. Moreover, immune labeling-activated macrophages enhanced antigen presentation at infection sites, further boosting specific T cell-mediated adaptive immune responses and infection eradication effects. Overall, this study illustrates a scalable bacteriophage immune therapy based on precise biological labeling and targeted modulation of immune responses, bridging the natural divide between bacteriophages and host immunity.
    DOI:  https://doi.org/10.1126/sciadv.adr1911
  11. Med Microbiol Immunol. 2025 Sep 02. 214(1): 40
    Antibiotic-resistant Acinetobacter baumannii can be killed by a combination of bacteriophages and complement.
    Carmen Chen, Eva Krzyżewska-Dudek, Sheetal Patpatia, Vinaya Dulipati, Sarah Natalia Mapelli, Aycan Meral, Juha Kotimaa, Saija Kiljunen, Seppo Meri.
      Infections caused by multidrug-resistant Acinetobacter baumannii are an emerging global health threat. Although phages have shown promising results in treating bacterial infections, the mechanisms of the combined effect of phages and innate immunity on clearing A. baumannii remain unclear. Here, we report a synergistic effect of the complement system and phages on clearing multidrug-resistant A. baumannii. We show that A. baumannii rapidly adapts and becomes resistant to phage or serum complement by modifying the expression of capsule and lipooligosaccharides, which can be regulated through reversible transposon mutagenesis in the K locus. Compared to the encapsulated phenotype, the non-encapsulated, phage-resistant A. baumannii showed a higher level of membrane attack complex deposition and were susceptible to killing by complement. In contrast, the encapsulated phenotype escaped the complement system by shedding the membrane attack complex to the environment. Thus, while the complement system targets the non-encapsulated phenotype, the phage infects and eliminates the encapsulated subpopulation. These results suggest means of combatting antibiotic-resistant A. baumannii by a simultaneous treatment with phages and complement, a combination which can be supplemented further with antibacterial antibodies.
    Keywords:   Acinetobacter baumannii ; Bacteriophage; Capsular polysaccharides; Complement system; Multidrug-resistant bacteria; Transposon mutagenesis
    DOI:  https://doi.org/10.1007/s00430-025-00852-0
  12. Front Microbiol. 2025 ;16 1614697
    Susceptibility profile of clinical and food-associated Listeria monocytogenes strains to a commercial phage product using different test methods.
    Christoph Brieske, Christina Böhnlein, Hui Zhi Low, Charles M A P Franz.
      Foodborne bacterial pathogens continue to pose a significant global health and economic burden, with Listeria monocytogenes being a persistent risk due to its frequent involvement in outbreaks and food recalls. Bacteriophage-based products are promising tools for enhancing food safety, yet systematic evaluations across genetically diverse L. monocytogenes strains are limited. In this study, we assessed the efficacy of a commercially available Listeria-specific phage product against 50 whole-genome-sequenced clinical and food-associated L. monocytogenes isolates recently collected in Germany. Traditional spot and plaque assays indicated 70-76% susceptibility, whereas viability-based methods, including colony reduction, OD600 measurement, and flow cytometry, demonstrated substantial bacterial reduction across all isolates within 24 h. Notably, flow cytometry revealed a marked decline in viable cells as early as 3 h post-treatment. By systematically comparing susceptibility assays, we argue that modern viability-based methods assessing microbial load reduction offer key advantages over classical plaque assays for evaluating phage efficacy in food safety applications. While plaque assays remain valuable primarily for determining infectivity, reduction-based approaches have the potential to serve as a measure of antimicrobial performance in biocontrol settings.
    Keywords:  Listeria monocytogenes; colony reduction; flow cytometry; optical density; phage P100; phage-susceptibility; plaque assay; spot assay
    DOI:  https://doi.org/10.3389/fmicb.2025.1614697
  13. Philos Trans R Soc Lond B Biol Sci. 2025 Sep 04. 380(1934): 20240075
    Capsid redirection mechanism of the Staphylococcus aureus pathogenicity island SaPIpT1028.
    Adaeze Doris Ojiogu, Jonasz B Patkowski, Xu Kuang, Tiago R D Costa, Jakob T Rostøl, José R Penadés.
      Staphylococcus aureus pathogenicity islands (SaPIs) are prototypical members of the phage-inducible chromosomal islands (PICI) family. These elements redirect helper phage capsid assembly to produce smaller capsids, accommodating the satellite genome while excluding the phage genome. This study identifies how SaPIpT1028 mediates capsid redirection through a unique gene, rcm (redirecting capsid morphogenesis). While rcm has no sequence similarity to known capsid assembly regulators, our results demonstrate that its expression is necessary and sufficient for redirecting capsid morphogenesis in S. aureus phages, such as φ7206. We show that, to do this, Rcm interacts with the φ7206 major capsid protein. Comparative evolutionary and structural analyses reveal functional parallels between Rcm and CpmB, a regulator used by other SaPIs. However, Rcm has evolved a multi-helical topology to match the multi-helical topology of the scaffold protein of φ7206. Sequence homology and AlphaFold predictions suggest that Rcm competitively interacts with the φ7206 scaffold protein, altering capsid size through a mechanism akin to CpmB. This work highlights SaPI adaptation, exemplified by Rcm's ability to exploit phages resistant to other remodellers, while inhibiting their reproduction. These findings underscore the dynamic co-evolution of phages and SaPIs, with Rcm playing a pivotal role in capsid size regulation and phage interference.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
    Keywords:  SaPI; gene transfer; phage
    DOI:  https://doi.org/10.1098/rstb.2024.0075
  14. Obstet Gynecol. 2025 Sep 04.
    Updates in Clinical Management of Recurrent Urinary Tract Infections.
    Nazema Y Siddiqui, Megan S Bradley.
      Urinary tract infections (UTIs) are common and burdensome in women. Here, we discuss challenges with our current models of care and how evolving insights into the female urogenital microbiome have advanced the understanding of how we diagnose, treat, and prevent recurrent UTIs in nonpregnant adult women. Traditional care models attribute recurrent UTIs mainly to gastrointestinal sources, resulting in significant emphasis on eradicating pathogens with potential overreliance on antibiotics. Evidence now shows that the bladder harbors a complex microbiome, with interactions between the urinary and vaginal environments and immune mechanisms at the bladder mucosal surface influencing infection susceptibility. Thus, in updated models of care, more emphasis is placed on enhancing the protective microbiome. This may be especially important in postmenopausal women, who experience microbiome shifts that increase vulnerability to recurrent infections, underscoring the role of estrogen therapy and microbiome-supportive interventions. Updated treatment approaches emphasize antimicrobial stewardship, advocating for confirmation of the diagnosis and delayed antibiotic initiation when safe, and judicious use of antibiotics for symptom relief. Prevention strategies highlight the importance of vaginal estrogen, methenamine salts, and other supplements rather than exclusive reliance on prophylactic antibiotics. Ongoing research into emerging therapies such as UTI vaccines and bacteriophage drugs may further decrease our reliance on antibiotics in the future. This clinical update underscores the need for individualized care plans that balance effective infection management while minimizing antibiotic-related harms, emphasizing a holistic, microbiome-centered approach to recurrent UTI prevention and treatment.
    DOI:  https://doi.org/10.1097/AOG.0000000000006060
  15. Folia Microbiol (Praha). 2025 Sep 01.
    Colistin resistance in the era of antimicrobial resistance: challenges and strategic countermeasures.
    Debasrita RoyChowdhury, Arnima Manna, Sukhendu Mandal, Poulami Mukherjee, Arnab Basu.
      Colistin resistance represents a mounting global health concern, particularly alarming in the face of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial infections. As a polymyxin-class antibiotic, colistin has long served as a critical last-line defence against severe Gram-negative infections caused by pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. However, its increasing and, at times, indiscriminate use has driven the emergence of resistant strains, thereby compromising its clinical utility.Mechanistically, colistin resistance arises from diverse genetic adaptations that alter the bacterial outer membrane, diminishing the drug's binding affinity. Prominent among these are modifications to lipopolysaccharides (LPS), including the incorporation of cationic groups that neutralise the membrane's negative charge, effectively impeding colistin interaction. In addition to chromosomal mutations, resistance is often mediated through horizontal gene transfer-most notably via mobile colistin resistance (mcr) genes-which facilitates rapid dissemination among bacterial populations.To counter this growing threat, innovative therapeutic strategies are urgently needed. These include the development of novel antibiotics with distinct mechanisms of action, synergistic combination regimens (e.g., colistin paired with potentiating agents), and the exploration of alternative modalities such as bacteriophage therapy. Gene-editing technologies like CRISPR-Cas9 also offer a promising frontier for targeting resistance determinants directly at the genetic level.Equally important are robust antimicrobial stewardship programmes and comprehensive surveillance systems to monitor resistance trends and guide rational antibiotic use. Ultimately, overcoming colistin resistance demands a multifaceted and integrative approach-one that merges scientific innovation with global public health initiatives.
    Keywords:  AMR; Colistin; Efflux pump; Mcr
    DOI:  https://doi.org/10.1007/s12223-025-01322-z
  16. Stat Biosci. 2025 Apr;17(1): 191-215
    DeepBiome: A Phylogenetic Tree Informed Deep Neural Network for Microbiome Data Analysis.
    Jing Zhai, Youngwon Choi, Xingyi Yang, Yin Chen, Kenneth Knox, Homer L Twigg, Joong-Ho Won, Hua Zhou, Jin J Zhou.
      Evidence linking the microbiome to human health is rapidly growing. The microbiome profile has the potential as a novel predictive biomarker for many diseases. However, tables of bacterial counts are typically sparse, and bacteria are classified within a hierarchy of taxonomic levels, ranging from species to phylum. Existing tools focus on identifying microbiome associations at either the community level or a specific, pre-defined taxonomic level. Incorporating the evolutionary relationship between bacteria can enhance data interpretation. This approach allows for aggregating microbiome contributions, leading to more accurate and interpretable results. We present DeepBiome, a phylogeny-informed neural network architecture, to predict phenotypes from microbiome counts and uncover the microbiome-phenotype association network. It utilizes microbiome abundance as input and employs phylogenetic taxonomy to guide the neural network's architecture. Leveraging phylogenetic information, DeepBiome is applicable to both regression and reduces the need for extensive tuning of the deep learning architecture, minimizes overfitting, and, crucially, enables the visualization of the path from microbiome counts to disease. It classification problems. Simulation studies and real-life data analysis have shown that DeepBiome is both highly accurate and efficient. It offers deep insights into complex microbiome-phenotype associations, even with small to moderate training sample sizes. In practice, the specific taxonomic level at which microbiome clusters tag the association remains unknown. Therefore, the main advantage of the presented method over other analytical methods is that it offers an ecological and evolutionary understanding of host-microbe interactions, which is important for microbiome-based medicine. DeepBiome is implemented using Python packages Keras and TensorFlow. It is an open-source tool available at https://github.com/Young-won/DeepBiome.
    Keywords:  Metagenomics; Mixed taxonomic levels; Neural networks; Phylogenetic tree; Prediction
    DOI:  https://doi.org/10.1007/s12561-024-09434-9
  17. Aesthetic Plast Surg. 2025 Sep 04.
    Rapid and Esthetic Wound Healing in Surgery by Applying a Powdered Mixture of Mannose and Calcium Propionate.
    Cristian Ionuţ Ciucanu, Sonia Raţiu, Sorin Olariu, Ionel Ciucanu.
       BACKGROUND: Wound healing is a current problem in surgery. Wounds most commonly occur from surgery, accidents, and burns. The purpose of this study was to reduce bleeding time and wound healing time as well as prevent or mitigate scarring by applying D-mannose with calcium propionate mixtures directly to the wound in powder form.
    METHODS: This study was a placebo, randomized, double-blind, crossover experiment involving a single group of twenty-five subjects. The number of incisions made was equal to the number of treatments required. Each subject had one incision per day. Only one treatment was applied to each wound. By the end, each subject was treated with all test mixtures and the placebo substance.
    RESULTS: The results show that the bleeding time can be reduced to about 50% compared to D-mannose when treating the wound with a mixture containing 20-60 moles of D-mannose per 1 mole of powdered calcium propionate. The wound healing time was reduced by about 40% compared to D-mannose. No visible scarring was observed after 40 days on skin treated with the mannose and calcium propionate mixture.
    CONCLUSIONS: Bleeding time can be reduced by approximately 50% when the wound is treated with a mixture containing 40 moles of D-mannose per 1 mole of calcium propionate and wound healing time by approximately 40% compared to D-mannose. Both substances contribute to the destruction of pathogens and to the processes of new tissue formation, which accelerates the healing process. Treatment with this powdered mixture prevents skin scarring.
    LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
    Keywords:  Bleeding time; Calcium propionate; D-Mannose; Esthetic wound healing; Skin; Surgery
    DOI:  https://doi.org/10.1007/s00266-025-05186-z
  18. J Food Prot. 2025 Aug 26. pii: S0362-028X(25)00157-7. [Epub ahead of print] 100605
    Commercial Bacteriophage Cocktail Treatment Reduces Salmonella Infantis Levels in Pre-Harvest Agricultural Water.
    Alan Gutierrez, Zirui Ray Xiong, Shayla B Johnson, Ajani A Brooks, Ellen Gabriel, Adib Adnan, Amit Vikram, Mary Theresa Callahan, Manan Sharma.
      Contaminated irrigation water in the pre-harvest environment can lead to outbreaks associated with fruits and vegetables. The potential of microbial contamination in pre-harvest waters by bacterial pathogens has created an ongoing demand for effective water treatment methods to mitigate this risk. This study sought to evaluate the efficacy of a commercial bacteriophage cocktail against Salmonella Infantis in agricultural water. A test agricultural water (TAW) medium prepared at different pH (6.5 and 8.4) and turbidity levels (4, 20, 50, and 100 NTU) was inoculated with a nalidixic acid resistant strain of S. Infantis (∼6 log CFU/mL), in triplicate trials, and treated with a bacteriophage cocktail (SalmoFresh™) at a phage titer of 8 log PFU/mL. Water samples were taken after a 5-minute contact time, with shaking (250 rpm), at 25°C. Additionally, collected pond water, natural (non-sterile) and autoclaved, was inoculated with S. Infantis (∼4 log CFU/mL) and treated with bacteriophage cocktail (7 log PFU/mL or 8 log PFU/mL) at either 12°C or 32°C for 5, 10, or 30 min in triplicate trials. Samples were enumerated by plating onto XLD or TSA supplemented with 50 μg/mL Nalidixic acid. In TAW, S. Infantis levels were reduced by an average of 1.0 log CFU/mL after the 5-minute phage treatment, with no significant differences in reductions across all pH and turbidity levels tested (p > 0.05). In pond water (natural and autoclaved), S. Infantis reductions only occurred when the phage titer was 8 log PFU/mL, with average reductions of 1.04, 1.50, and 1.67 log CFU/mL after 5, 10, and 30 min, respectively, at 32°C. At 12°C, average reductions were 0.90, 1.15, and 1.36 log CFU/mL after 5, 10, and 30 min, respectively. These results demonstrate that commercial lytic phage cocktail specific for Salmonella are effective in water across various conditions (pH, turbidity, temperature) and may be considered with other technologies to reduce Salmonella levels in agricultural water.
    Keywords:  Salmonella; agricultural water; bacteriophage; irrigation; water treatment
    DOI:  https://doi.org/10.1016/j.jfp.2025.100605
  19. PLoS One. 2025 ;20(8): e0330765
    Visualization of multidrug-resistant bacterial infection trends in the intensive care units.
    Woojae Jeon, Yu-Mi Lee, Dong Youn Kim, Ki-Ho Park, Mi Suk Lee.
       BACKGROUND: The Korean National Healthcare-associated Infections Surveillance System (KONIS) monitors multidrug-resistant (MDR) bacterial infections in intensive care units (ICUs). However, simultaneously monitoring hundreds of ICUs remains challenging. Our study aimed to visualize the trends of MDR gram-negative bacterial infections in ICUs monitored by KONIS.
    METHODS: We evaluated KONIS data from 137 ICUs (2006-2011) and from 368 ICUs (2017-2022). Pneumonia, urinary tract infection, and bloodstream infection caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii were analyzed. Transformation was employed to convert the infection rate graphs of each ICU into arrows. The length and angle of the arrows reflect changes in carbapenem susceptibility and infection rate, respectively. ICUs are categorized into red (rapid shift from susceptible to resistant bacteria and increased infection rate), yellow (slow shift from susceptible to resistant bacteria and decreased infections rate), and green (shift from resistant to susceptible bacteria) groups. The proportional changes in each ICU category were compared during the first and last five years of the study periods.
    RESULTS: For K. pneumoniae, the proportion of red category ICUs increased (0% to 17%, p-value 0.586), while the proportions of yellow (33.3% to 7%, p-value 0.288) and green category ICUs (66.6% to 36%, p-value 0.290) decreased. For P. aeruginosa, the proportions of red (12% to 27%, p-value 0.016) and green category ICUs (38% to 46%, p-value 0.358) increased, while the proportion of yellow category ICUs decreased (8% to 2%, p-value 0.043). For A. baumannii, the proportions of red (19% to 14%, p-value 0.649) and yellow category ICUs (5% to 1%, p-value 0.187) decreased, while the proportion of green category ICUs increased (19% to 72%, p-value <0.001).
    CONCLUSIONS: Graph transformation allowed the observation of MDR Gram-negative bacterial infection trends in ICUs. Further studies should aim to confirm whether our arrow indicators are useful for infection control and in identifying factors for reducing infections.
    DOI:  https://doi.org/10.1371/journal.pone.0330765
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