bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–04–13
29 papers selected by
Luca Bolliger, lxBio



  1. PLoS Pathog. 2025 Apr;21(4): e1012971
      Klebsiella pneumoniae (KP) is a Gram-negative bacterium that commonly resides in the human gastrointestinal tract and can also act as an opportunistic pathogen and cause extra-intestinal infections. KP poses a global health threat because it causes both hospital- and community-acquired infections in immune-competent and immunocompromised hosts. These infections can be multidrug-resistant and/or hypervirulent, making KP infections difficult to treat and deadly. In the absence of effective treatments for recalcitrant KP infections, bacteriophage (phage) therapy is gaining attention as a promising alternative. In this review, we evaluate KP epidemiology and epitope diversity, discuss interactions between KP-targeting phages and their bacterial hosts from an eco-evolutionary perspective, and summarize recent efforts in phage therapy for treating KP infections. We also discuss novel approaches, including genetic engineering and machine learning, as initial steps toward developing KP-targeting phage therapy as a precision medicine approach for an emerging and dangerous pathogen.
    DOI:  https://doi.org/10.1371/journal.ppat.1012971
  2. Int J Antimicrob Agents. 2025 Apr 09. pii: S0924-8579(25)00065-2. [Epub ahead of print] 107508
       PURPOSE: The objective of this study is to examine the efficacy of bacteriophage therapy in combating Acinetobacter baumannii, a pathogen known for its multidrug resistance, through the application of Bayesian statistical models. The research focuses on measuring survival outcomes in preclinical animal models that have been treated with bacteriophages, highlighting the promise of Bayesian methods in tackling the uncertainties present in biological data.
    METHODOLOGY: We carried out a systematic review, focusing on identifying pertinent studies regarding phage therapy in animal models. Bayesian exploratory data analysis (EDA) was utilized to evaluate survival rates among three species: rodents, Galleria mellonella, and zebrafish. Various prior distributions were utilized in sensitivity analyses to assess the reliability of the results.
    RESULTS: The study showed that groups that were treated with phage therapy had much higher survival rates across all experimental models. In untreated groups, survival rates for rodents ranged from 20% to 40%, while treated groups saw an increase to between 60% and 80%. Survival rates went up in the Galleria mellonella and zebrafish models. They went from 30% to 50% in the untreated groups to 70% to 90% and 70% to 80%, respectively, in the treated groups. The analysis demonstrated the reliability of these findings, showing consistent survival advantages across different prior assumptions.
    PRACTICAL IMPLICATIONS: The results support the clinical development of phage therapy as a possible way to treat infections that are resistant to multiple drugs. The use of Bayesian methods provides a strong foundation for assessing therapeutic effectiveness, especially in situations where conventional statistical approaches might fall short.
    ORIGINALITY/VALUE: In this study, Bayesian methods are used in a new way to figure out how well phage therapy works. This shows that they can handle variation and uncertainty in preclinical studies. This research adds to the increasing body of evidence that highlights phage therapy as a viable alternative to traditional antibiotics.
    Keywords:  Acinetobacter baumannii; Bacteriophage therapy; Bayesian analysis; multidrug resistance; preclinical models
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107508
  3. Foodborne Pathog Dis. 2025 Apr 11.
      Bacteriophage engineering is a promising strategy to address multidrug-resistant (MDR) bacterial infections that pose significant challenges to public health due to the overuse of antibiotics. Bacteria can develop resistance mechanisms, such as receptor modification and activation of antiviral defense systems, which further complicates the application of phage therapy. Additionally, long-term phage therapy can result in the production of anti-phage antibodies, which may interfere with treatment. These factors require advanced engineering techniques to improve the efficacy of phages and expand their host range. Recent advances in genome engineering methods, including CRISPR/Cas9, homologous recombination, and other synthetic biology techniques, offer promising solutions to these challenges. By modifying receptor-binding proteins and using high-yield screening methods, researchers can create phages that are better equipped to target MDR bacteria effectively. Furthermore, understanding the intricate interactions between phages and their bacterial hosts is critical to guiding these engineering efforts. Future development perspectives lie in integrating these advanced engineering techniques into clinical practice, potentially putting bacteriophages at the forefront of fighting MDR bacterial infections.
    Keywords:  CRISPR; bacteriophage engineering; homologous recombination; multidrug-resistant bacteria
    DOI:  https://doi.org/10.1089/fpd.2024.0194
  4. Microbiol Spectr. 2025 Apr 09. e0114524
      Multidrug-resistant (MDR) Klebsiella pneumoniae is challenging to treat with conventional antibiotic regimens, posing a threat to healthcare systems. Phage therapy presents a promising alternative treatment strategy; however, characterization of its efficacy and safety is required. Here, we describe the microbiological and molecular characterization of a novel bacteriophage with activity against MDR K. pneumoniae using a greater wax moth (Galleria mellonella) model system. A bacteriophage was isolated from hospital wastewater. Viral kinetics and phage stability were evaluated under varied pH and temperature conditions. The therapeutic efficacy of the phage was evaluated using MDR Klebsiella-infected G. mellonella larvae as an in vivo model. Phage titers and larva survival were compared in phage-treated and control groups. Genomic sequencing (Nanopore and Illumina) was used to classify the bacteriophage and identify any resistance genes or virulence factors present in its genome. Functional characterization demonstrated effective lytic activity, favorable burst size (161 PFU/cell), and an optimal MOI of 0.1. The phage demonstrated stability across a wide range of temperatures (8°C-40°C) and pH levels (4-8). Experiments using the G. mellonella model showed improved larval survival with phage treatment. The novel bacteriophage was identified as a new species within the genus Drulisvirus with no lysogeny-associated, antimicrobial resistance, or virulence genes detected. The new Drulisvirus phage identified is a promising candidate for treatment of infections caused by MDR K. pneumoniae.IMPORTANCEThe study describes a bacteriophage with potential for use in phage therapy against Klebsiella pneumoniae, one of the most clinically significant bacterial pathogens today. Microbiological and genomic characterization of the phage revealed advantageous properties for therapeutic applications, while also identifying a novel species within the Drulisvirus genus. These findings significantly contribute to our understanding of bacteriophage diversity and their utility in combating antibiotic-resistant infections. Moreover, the authors developed an in vivo preclinical model of MDR infection using Galleria mellonella larvae and successfully applied it to study the bacteriophage's therapeutic efficacy. This model offers a robust and efficient platform for preclinical testing.
    Keywords:  Galleria mellonella; Klebsiella pneumoniae; bacteriophages; phage therapy
    DOI:  https://doi.org/10.1128/spectrum.01145-24
  5. mSystems. 2025 Apr 08. e0136424
      The human gut virome is predominantly made up of bacteriophages (phages), viruses that infect bacteria. Metagenomic studies have revealed that phages in the gut are highly individual specific and dynamic. These features make it challenging to perform meaningful cross-study comparisons. While several taxonomy frameworks exist to group phages and improve these comparisons, these strategies provide little insight into the potential effects phages have on their bacterial hosts. Here, we propose the use of predicted phage host families (PHFs) as a functionally relevant, qualitative unit of phage classification to improve these cross-study analyses. We first show that bioinformatic predictions of phage hosts are accurate at the host family level by measuring their concordance to Hi-C sequencing-based predictions in human and mouse fecal samples. Next, using phage host family predictions, we determined that PHFs reduce intra- and interindividual ecological distances compared to viral contigs in a previously published cohort of 10 healthy individuals, while simultaneously improving longitudinal virome stability. Lastly, by reanalyzing a previously published metagenomics data set with >1,000 samples, we determined that PHFs are prevalent across individuals and can aid in the detection of inflammatory bowel disease-specific virome signatures. Overall, our analyses support the use of predicted phage hosts in reducing between-sample distances and providing a biologically relevant framework for making between-sample virome comparisons.
    IMPORTANCE: The human gut virome consists mainly of bacteriophages (phages), which infect bacteria and show high individual specificity and variability, complicating cross-study comparisons. Furthermore, existing taxonomic frameworks offer limited insight into their interactions with bacterial hosts. In this study, we propose using predicted phage host families (PHFs) as a higher-level classification unit to enhance functional cross-study comparisons. We demonstrate that bioinformatic predictions of phage hosts align with Hi-C sequencing results at the host family level in human and mouse fecal samples. We further show that PHFs reduce ecological distances and improve virome stability over time. Additionally, reanalysis of a large metagenomics data set revealed that PHFs are widespread and can help identify disease-specific virome patterns, such as those linked to inflammatory bowel disease.
    Keywords:  bacteriophages; bioinformatics; gut microbiome; microbial interactions; virome
    DOI:  https://doi.org/10.1128/msystems.01364-24
  6. Nat Rev Microbiol. 2025 Apr 10.
      A comprehensive analysis of the clinical antibacterial pipeline demonstrates that there is a limited range of strategies that are primarily focused on modified versions of widely used chemical classes. These modifications aim to circumvent class-specific resistance mechanisms and reduce resistance rates in certain multidrug-resistant pathogens. Owing to the great variation in resistance rates and mechanisms, the clinical success of current approaches varies substantially across different countries, regions, and economic and environmental conditions, which affects the global societal value of these antibiotics that remain vulnerable to cross-resistance. Although there has been some progress in developing urgently needed antibiotics with novel targets and chemical structures, some of which have advanced to phase I/II trials, further breakthroughs are required. Additionally, adjunctive agents designed to enhance the outcome of conventional antibiotic therapies, along with bacteriophages that offer targeted and personalized treatments, are also under investigation. However, the potential of adjunctive therapeutics, such as antivirulence agents, and bacteriophages has yet to be realized in terms of feasibility and global societal impact.
    DOI:  https://doi.org/10.1038/s41579-025-01169-8
  7. J Res Med Sci. 2025 ;30 2
      The gut ecosystem, comprising the gut microbiota and its interactions, plays a crucial role in human health and disease. This complex ecosystem involves a diverse array of microorganisms such as viruses, fungi, and bacteria, collectively known as the gut microbiota. These microorganisms contribute to various functions, including nutrient metabolism and immune modulation, thereby impacting human health. Dysbiosis, or an imbalance in the gut microbiota, has been associated with the pathogenesis of several diseases, ranging from intestinal disorders such as inflammatory bowel disease to extra-intestinal conditions such as metabolic and neurological disorders. The implications of dysbiosis in the gut ecosystem are far-reaching, affecting not only gastrointestinal health but also contributing to the development and progression of conditions such as autoimmune gastritis and gastric cancer. Furthermore, the burden of antimicrobial use and subsequent side effects, including antibiotic resistance, poses additional challenges in managing gastrointestinal diseases. In light of these complexities, investigating the role of bacteriophages as regulators of the gut ecosystem and their potential clinical applications presents a promising opportunity to tackle antibiotic resistance and fight infectious diseases.
    Keywords:  Bacteria; bacteriophage; gastroenteritis; gastrointestinal diseases
    DOI:  https://doi.org/10.4103/jrms.jrms_464_24
  8. PLoS Biol. 2025 Apr;23(4): e3003063
      Research on bacteriophages, the viruses infecting bacteria, has fueled the development of modern molecular biology and inspired their therapeutic application to combat bacterial multidrug resistance. However, most work has so far focused on a few model phages which impedes direct applications of these findings in clinics and suggests that a vast potential of powerful molecular biology has remained untapped. We have therefore recently composed the BASEL collection of Escherichia coli phages (BActeriophage SElection for your Laboratory), which made a relevant diversity of phages infecting the E. coli K-12 laboratory strain accessible to the community. These phages are widely used, but their assorted diversity has remained limited by the E. coli K-12 host. We have therefore now genetically overcome the two major limitations of E. coli K-12, its lack of O-antigen glycans and the presence of resident bacterial immunity. Restoring O-antigen expression resulted in the isolation of diverse additional viral groups like Kagunavirus, Nonanavirus, Gordonclarkvirinae, and Gamaleyavirus, while eliminating all known antiviral defenses of E. coli K-12 additionally enabled us to isolate phages of Wifcevirus genus. Even though some of these viral groups appear to be common in nature, no phages from any of them had previously been isolated using E. coli laboratory strains, and they had thus remained largely understudied. Overall, 37 new phage isolates have been added to complete the BASEL collection. These phages were deeply characterized genomically and phenotypically with regard to host receptors, sensitivity to antiviral defense systems, and host range. Our results highlighted dominant roles of the O-antigen barrier for viral host recognition and of restriction-modification systems in bacterial immunity. We anticipate that the completed BASEL collection will propel research on phage-host interactions and their molecular mechanisms, deepening our understanding of viral ecology and fostering innovations in biotechnology and antimicrobial therapy.
    DOI:  https://doi.org/10.1371/journal.pbio.3003063
  9. ISME J. 2025 Apr 06. pii: wraf065. [Epub ahead of print]
      Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis, dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics. A single administration of phages effectively reduced P. aeruginosa viability in planktonic conditions and infected human lung cell cultures, but phage-resistant variants subsequently emerged. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and meropenem antibiotic. In contrast, adherent biofilms showed tolerance to phage and/or meropenem, suggesting a spatio-temporal variation in the phage-bacterial interaction. The kinetics of adsorption of each phage to P. aeruginosa during single- or co-administration were comparable. However, the phage with the shorter lysis time depleted bacterial resources early and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage. The extent and strength of this phage-phage competition and genetic loci conferring phage resistance, are, however, P. aeruginosa genotype dependent. Nevertheless, adding phages sequentially resulted in their unimpeded replication with no significant increase in bacterial host lysis. These results highlight the interrelatedness of phage-phage competition, phage resistance and specific bacterial growth state (planktonic/biofilm) in shaping the interplay among P. aeruginosa and virulent phages.
    Keywords:  Bacteria-phage interactions; Cystic fibrosis; Phage resistance; Phage therapy; Phage-phage competition; Pneumonia
    DOI:  https://doi.org/10.1093/ismejo/wraf065
  10. Phys Rev Lett. 2025 Mar 28. 134(12): 128402
      Phages and bacteria coexist under widely different conditions, ranging from liquid cultures to oceans, soil, and the human gut. However, our models are typically limited to well-mixed liquid cultures governed by mass-action kinetics. Here, we suggest a modification to the Lotka-Volterra dynamics by including the formation of microcolonies. By analyzing the model in an open system with a steady influx of bacteria, we predict that the colony size distribution is power-low distributed with steeper exponents for the stronger external influx. In the realistic case where the phage attack rate to individual colonies is proportional to their radius, we obtain self-organization to a steady state where the maximal colony size is smaller for stronger external driving.
    DOI:  https://doi.org/10.1103/PhysRevLett.134.128402
  11. ACS Omega. 2025 Apr 01. 10(12): 12026-12036
      The surge in antibiotic-resistant Staphylococcus aureus infections has been deemed a major public health concern. There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting S. aureus was examined. Pleurotin was isolated from the basidiomycota fungus Hohenbuehelia grisea. The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two S. aureus strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.
    DOI:  https://doi.org/10.1021/acsomega.4c09831
  12. Nanomedicine (Lond). 2025 Apr 09. 1-16
      Bacterial infections in the blood (sepsis) have been recognized as a leading cause of mortality in the clinical field due to limitations in the detection of bacteria at low concentration and their resistance to antibiotics by excessive misuse. Some of the common symptoms are fever, chills, rapid heartbeat, difficulty breathing, confusion, and changes in mental status with occasionally pale, clammy, and mottled skin. Early diagnosis and identification are the keys to a successful treatment for sepsis patients. Researchers have developed nanoparticles to enrich bacterial populations followed by detection and applied them to conventional methods such as phenotypic and molecular diagnostics to enhance different detectors' responses toward pathogens. This short review systematically overviews steps that are followed in clinical labs for bacterial detection, identification, and their drawbacks. In this context, we discuss the role that nanoparticles can play in overcoming the limits of traditional microbiology methods in terms of turnaround times (TATs) and accuracy. We believe that this short review will provide up-to-date information about the applications of nanoparticles in the enrichment, separation, and identification of bacterial infection in the clinical field and, therefore, a way of rapid treatment.
    Keywords:  MLADI-TOF; Sepsis; blood culture; enrichment; nanosystems; turnaround times
    DOI:  https://doi.org/10.1080/17435889.2025.2488724
  13. Future Microbiol. 2025 Apr 10. 1-9
       AIM: Increasing resistance among ESKAPEEc pathogens, particularly Acinetobacter baumannii and Pseudomonas aeruginosa, has necessitated the use of last-resort antibiotics such as colistin. This study aimed to evaluate the effectiveness and reveal a dynamic picture of colistin-based combination therapies.
    MATERIALS & METHODS: This study evaluated the in vitro efficacy of colistin in combination with doxycycline, doripenem, and rifampicin against multidrug-resistant clinical isolates of P. aeruginosa (n = 23) and A. baumannii (n = 26). Susceptibility testing performed by microbroth dilution method, and synergistic interactions were assessed via checkerboard and time-kill curve (TKC) assays.
    RESULTS: All isolates were resistant to colistin, according to their MICs. In checkerboard assays, according to synergism rates, colistin-doripenem and colistin-doxycycline combinations were particularly effective. The degrees of synergy for doripenem, doxycycline, and rifampicin were 30%, 90%, and 20%, respectively, against P. aeruginosa, and 30%, 60%, and 30%, respectively, against A. baumannii. In TKC analysis, synergistic interactions are generally observed with colistin at 1/4×MIC or 1×MIC, and indifference effects at 4×MIC, similar to colistin monotherapy. TKCs also confirmed the bactericidal activities of combinations that achieved ≥3-log10 reductions in initial bacterial counts.
    CONCLUSIONS: Colistin-based combination therapies, especially colistin-doripenem, may be promising approaches for combating multidrug-resistant pathogens while potentially reducing nephrotoxicity risk.
    Keywords:  A. baumannii; Colistin; P. aeruginosa; doripenem; doxycycline; rifampicin
    DOI:  https://doi.org/10.1080/17460913.2025.2490377
  14. Appl Environ Microbiol. 2025 Apr 10. e0207024
      Pseudogenes are regarded as "junk" DNA, representing vestigial functions no longer needed for fitness. Accordingly, a higher number of pseudogenes in a bacterial human pathogen was previously hypothesized to be a hallmark of host specialists. In this study, we tested this hypothesis on the emergent bacterial plant pathogen Xylella fastidiosa (Xf) to link pseudogene makeup and host specificity. Xf is an ideal subject for these studies by being a xylem-limited pathogen that underwent extensive genome reduction. Using natural host range data of 151 strains and Pseudofinder analysis on Xf whole genome sequences, we observed that Xf subsp. sandyi had the highest pseudogene content, followed by subsp. morus, while subsp. pauca, fastidiosa, and multiplex had the lowest. The first two subspecies are known to have a limited host range compared to the others, aligning with the hypothesis of a greater number of pseudogenes corresponding to narrower host range. Weed isolates are presumably host specialists because they had the highest pseudogene content. Using a thorough pseudogene map across genomes and empirical pathogenicity data on blueberries, we screened for genes potentially involved in blueberry specialization. Targets were identified by selecting sequences pseudogenized (i) in strains infecting hosts different from blueberry and (ii) only in blueberry asymptomatic strains. Six sequences were identified with a potential role in blueberry infection, including one that was common between the two criteria. Here, we generated hypotheses on host range and specificity of Xf strains that need to be tested experimentally to help understand this devastating plant pathogen.IMPORTANCEXylella fastidiosa is a highly destructive plant pathogen that infects hundreds of landscape and agriculturally important plant species mainly in Europe and the Americas. Nevertheless, the host range of specific genotypes and underlying mechanisms of host specificity remain unclear. These are important aspects to determine the potential risk of infection in specific areas depending on the genetic makeup of the pathogen population and hosts present. This study offers valuable insights into the role of pseudogenization in the genomes of different X. fastidiosa strains, linking it to host specialization. Despite the limited information available for the host range of different strains of this pathogen, this research proposes a relationship between the abundance of pseudogenes and host specificity. These findings are essential for predicting potential host shifts by this pathogen, aiding in the development of strategies to prevent its spread. Additionally, the identification of candidate genes putatively important for symptom development in blueberries offers targets for prevention and control efforts.
    Keywords:  Pseudofinder; host generalists; host range; host specialist; intergenic; weeds
    DOI:  https://doi.org/10.1128/aem.02070-24
  15. PLoS Biol. 2025 Apr 08. 23(4): e3003065
      Growth rate plays a fundamental role in microbiology and serves as an important proxy for fitness in evolution. While high-throughput measurements of bacterial growth rates are easily performed in any microbiology laboratory, similar methods are lacking for bacteriophages. This gap hinders systematic comparisons of important phage phenotypes, such as their amplification rate in bacterial populations and their bactericidal effect, across different phages and environmental conditions. Here, we show that the amplification rate of lytic phages can be quantified by analyzing bacterial population growth and collapse dynamics under phage predation using a parsimonious mathematical model - an approach termed Phage-Host Observation for Rate estimation from Collapse Events (PHORCE). We found that the resulting phage amplification rate captures the bactericidal effect independent of initial phage and bacterial population sizes for fast-growing hosts and adsorption-limited phages. Using high-throughput PHORCE, we found that the amplification rates of Escherichia coli phages vary widely by more than three orders of magnitude. Furthermore, our approach suggests that phage-antibiotic interactions are predominantly determined by the antibiotic, and not by the phage. In particular, the ribosome-inhibiting antibiotic doxycycline generally showed antagonism with phage amplification, whereas the DNA-damaging antibiotic nitrofurantoin was synergistic. This framework provides a means to quantitatively characterize phage phenotypes and may facilitate future high-throughput phage screens for antibacterial applications.
    DOI:  https://doi.org/10.1371/journal.pbio.3003065
  16. Clin Exp Med. 2025 Apr 05. 25(1): 107
      Inflammatory bowel disease (IBD) is a multifactorial illness with a climbing prevalence worldwide. While biologics are commonly prescribed especially for severe cases, they may worsen patients' outcomes due to financial burden. Consequently, there has been an increased focus on biosimilars to improve overall disease outcomes by maintaining similar efficacy and safety while minimizing the cost of therapy. Infliximab-dyyb was the first biosimilar approved by US-FDA for IBD. Since that, the US-FDA approved 14 biosimilars with different mechanisms of action and different routes of administration for IBD patients (four infliximab biosimilars, nine adalimumab biosimilars, and most recently one ustekinumab biosimilar). It should be noted that more biologics are in the pipeline as golimumab and natalizumab patents are set to expire in the near future, and biosimilars are now in pre-clinical to phase 3 trials. Different studies have evaluated biologics' effectiveness and safety and concluded that the majority of available biosimilars are efficacious and have similar adverse effect profiles compared to their reference biologics. It is worth mentioningthat post-marketing surveillance reports revealed some risks associated with biosimilars which should be taken into consideration in future research and clinical trials to avoid health hazards. Most biologics and biosimilars are administered parenterally which results in several drawbacks such as raised risk of infections, hypersensitivity, autoimmunity, development of malignancies, liver toxicity as well as worsening of heart failure. Several drug delivery systems based on passive and active targeting mechanisms are under active investigation to overcome these limitations. This review sheds light on the emergence of biologics and biosimilars as alternatives in IBD management, the differences between them, challenges and risks, and future perspectives in IBD therapy and new trends in drug delivery systems.
    Keywords:  Adalimumab; Biologics; Biosimilars; Drug delivery system; Inflammatory bowel disease; Infliximab; Ustekinumab
    DOI:  https://doi.org/10.1007/s10238-025-01558-6
  17. J Antimicrob Chemother. 2025 Apr 10. pii: dkaf109. [Epub ahead of print]
      Gonorrhoea constitutes a global public health threat. Although a range of antibiotics have been available to treat gonococcal infections for more than 80 years, Neisseria gonorrhoeae has shown remarkable versatility in its ability to develop resistance to successive classes of drugs. As a result, national and international treatment guidelines have had to be regularly updated to take account of increases in the prevalence of gonococcal strains resistant to recommended antibiotics. Even when particular antibiotics are no longer empirically used to treat gonorrhoea, N. gonorrhoeae often retains resistance, with strains becoming MDR over time. Future efforts to ensure gonorrhoea remains a treatable infection will require a multidisciplinary global approach including efforts to provide widely available and affordable diagnostic testing, robust international surveillance of resistance, and the development of new antibiotics coupled with enhanced antimicrobial stewardship to ensure optimal use of both new and older antimicrobial agents.
    DOI:  https://doi.org/10.1093/jac/dkaf109
  18. Crit Rev Microbiol. 2025 Apr 10. 1-20
      Antimicrobial resistance (AMR) poses a significant public health threat, with emerging and novel forms of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB) potentially crossing international borders and challenging the global health systems. The rate of development of antibiotic resistance surpasses the development of new antibiotics. Consequently, there is a growing threat of bacteria acquiring resistance even to newer antibiotics further complicating the treatment of bacterial infections. Horizontal gene transfer (HGT) is the key mechanism for the spread of antibiotic resistance in bacteria through the processes of conjugation, transformation, and transduction. Several compounds, other than antibiotics, have also been shown to promote HGT of ARGs. Given the crucial role of HGT in the dissemination of ARGs, inhibition of HGT is a key strategy to mitigate AMR. Therefore, this review explores the contribution of HGT in bacterial evolution, identifies specific hotspots andhighlights the role of HGT inhibitors in impeding the spread of ARGs. By specifically focusing on the HGT mechanism and its inhibition, these inhibitors offer a highly promising approach to combating AMR.
    Keywords:  HGT inhibitors; Horizontal gene transfer; antimicrobial resistance; conjugation; transformation
    DOI:  https://doi.org/10.1080/1040841X.2025.2489463
  19. Microbiol Spectr. 2025 Apr 10. e0198124
      The beetle family Ptinidae contains a number of economically important pests, such as the cigarette beetle Lasioderma serricorne, the drugstore beetle Stegobium paniceum, and the diverse spider beetles. Many of these species are stored product pests, which target a diverse range of food sources, from dried tobacco to books made with organic materials. Despite the threat that the 2,200 species of Ptinidae beetles pose, fewer than 50 have been surveyed for microbial symbionts, and only a handful have been screened using contemporary genomic methods. In this study, we screen 116 individual specimens that cover most subfamilies of Ptinidae, with outgroup beetles from closely related families Dermestidae, Endecatomidae, and Bostrichidae. We used 16S ribosomal RNA gene amplicon data to characterize the bacterial microbiomes of these specimens. The majority of these species had never been screened for microbes. We found that, unlike in their sister family, Bostrichidae, that has two mutualistic bacteria seen in most species, there are no consistent bacterial members of ptinid microbiomes. For specimens which had Wolbachia infections, we did additional screening using multilocus sequence typing and showed that our populations have different strains of Wolbachia than noted in previous publications.
    IMPORTANCE: Ptinid beetles are both household pests of pantry goods and economic pests of dried goods warehouses and cultural archives, such as libraries and museums. Currently, the most common pest control measures for ptinid beetles are phosphine and/or heat treatments. Many ptinid beetles have been observed to have increasing resistance to phosphine, and heat treatments are not appropriate for many of the goods commonly infested by ptinids. Pest control techniques focused on symbiotic bacteria have been shown to significantly decrease populations and often have the beneficial side effect of being more specific than other pest control techniques. This survey provides foundational information about the bacteria associated with diverse ptinid species, which may be used for future control efforts.
    Keywords:  Anobiidae; Bostrichidae; Bostrichoidea; Dermestidae; Ptinidae; Sodalis; Wolbachia
    DOI:  https://doi.org/10.1128/spectrum.01981-24
  20. Infect Dis Ther. 2025 Apr 10.
      Healthcare-associated infections (HAIs), previously known as nosocomial infections, represent a significant threat to healthcare systems worldwide, prolonging patient hospital stays and the duration of antimicrobial therapy. One of the most serious consequences of HAIs is the increase in the rate of antibiotic resistance (AR) generated by the prolonged, frequent, and sometimes incorrect use of antibiotics, which leads to the selection of resistant bacteria, making treatment difficult and expensive, with direct consequences for the safety of patients and healthcare personnel. Therefore, timely and accurate diagnosis of HAIs is mandatory to develop appropriate infection prevention and control practices (IPC) and new therapeutic strategies. This review aimed to present the prevalence, risk factors, current diagnosis, including artificial intelligence (AI) and machine learning approaches, future perspectives in combating HAIs causative bacteria (phage therapy, microbiome-based interventions, and vaccination), and HAIs surveillance strategies. Also, we discussed the latest findings regarding the relationships of AR with climate change and environmental pollution in the context of the One Health approach. Phage therapy is an emerging option that can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria causing HAIs. Clinical trials dealing with vaccine development for resistant bacteria have yielded conflicting results. Two promising strategies, fecal microbiota transplantation and probiotic therapy, proved highly effective against recurrent Clostridium difficile infections and have been shown to reduce HAI incidence in hospitalized patients undergoing antibiotic therapy. Artificial intelligence and machine learning systems offer promising predictive capabilities in processing large volumes of clinical, microbiological, and patient data but require robust data integration. Our paper argues that HAIs are still a global challenge, requiring stringent IPC policies, computer vision, and AI-powered tools. Despite promising avenues like integrated One Health approaches, optimized phage therapy, microbiome-based interventions, and targeted vaccine development, several knowledge gaps in clinical efficacy, standardization, and pathogen complexity remain to be answered.
    Keywords:  Dysbiosis; Hospital-acquired infections; Microbiome; Multidrug resistant; One-Health; Phage therapy; Vaccines
    DOI:  https://doi.org/10.1007/s40121-025-01143-0
  21. Vet Clin North Am Food Anim Pract. 2025 Apr 04. pii: S0749-0720(25)00015-5. [Epub ahead of print]
      Veterinary engagement in development of selective treatment protocols for non-severe clinical mastitis has numerous advantages for clients. Selective treatment protocols restrict antimicrobial treatments to cases that will benefit from antimicrobial therapy while depending on the immune response to clear many intramammary infections. Veterinarians should help clients develop selective treatment protocols that are based on determination of etiology and review of cow-level factors that influence immune capabilities. Effective use of selective treatment protocols is cost-effective and socially responsible and results in 25% to 50% reductions in unnecessary antimicrobial usage on dairy farms.
    Keywords:  Antibiotics; Bovine; Dairy cow; Mastitis; Therapy; Treatment
    DOI:  https://doi.org/10.1016/j.cvfa.2025.02.003
  22. Methods Mol Biol. 2025 ;2898 3-21
      Wheat leaf rust, caused by Puccinia triticina Eriks., is one of the most widespread and destructive diseases of wheat in Canada and worldwide. Commonly used control measures include host genetic resistance and fungicide application. Genetic resistance has proven to be very effective and can also be durable when the right combinations of resistance genes are incorporated into wheat cultivars. However, P. triticina is a highly variable pathogen with diverse populations over large geographic areas. This often leads to the evolution of virulence toward resistance genes that are widely used in wheat cultivars. These virulent races are then rapidly selected by wheat cultivars that depend on these now ineffective resistance genes for protection. It is critical to detect these virulent races as quickly as possible to alert producers when some cultivars which were formerly resistant are now susceptible so that they can switch to other, more resistant cultivars or chemical control options. Similarly, wheat breeders need to be alerted that certain resistance genes and cultivars have lost their effectiveness to enable them to select alternative resistance genes and gene combinations for which virulence has not been detected. The purpose of this chapter is to describe the detailed methods required to reliably determine the virulence phenotype, or race, for isolates of P. triticina.
    Keywords:  Avirulence; Isolate; Race; Resistance; Rust; Virulence
    DOI:  https://doi.org/10.1007/978-1-0716-4378-5_1
  23. Front Microbiol. 2025 ;16 1591189
      
    Keywords:  Phage (bacteriophage); Salmonella; Salmonella infection models; Salmonella serovar; phage therapy
    DOI:  https://doi.org/10.3389/fmicb.2025.1591189
  24. Appl Environ Microbiol. 2025 Apr 09. e0041525
      Enterococci are lactic acid bacteria (LAB) that, as their name implies, often are found in the gastrointestinal tract of animals. Like many other gut-dwelling LAB, for example, various lactobacilli, they are frequently found in other niches as well, including plants and fermented foods from all over the world. In fermented foods, they contribute to flavor and other organoleptic properties, help extend shelf life, and some even possess probiotic properties. There are many positive attributes of enterococci; however, they have been overshadowed by the occurrence of antibiotic-resistant and virulent strains, often reported for the two species, Enterococcus faecalis and Enterococcus faecium. More than 40,000 whole-genome sequences covering 64 Enterococcus type species are currently available in the National Center for Biotechnology Information repository. Closer inspection of these sequences revealed that most represent the two gut-dwelling species E. faecalis and E. faecium. The remaining 62 species, many of which have been isolated from plants, are thus quite underrepresented. Of the latter species, we found that most carried no potential virulence and antibiotic resistance genes, an observation that is aligned with these species predominately occupying other niches. Thus, the culprits found in the Enterococcus genus mainly belong to E. faecalis, and a biased characterization has resulted in the opinion that enterococci do not belong in food. Since enterococci possess many industrially desirable traits and frequently are found in other niches besides the gut of animals, we suggest that their use as food fermentation microorganisms is reconsidered.IMPORTANCEWe have retrieved a large number of Enterococcus genome sequences from the National Center for Biotechnology Information repository and have scrutinized these for the presence of virulence and antibiotic resistance genes. Our results show that such genes are prevalently found in the two species Enterococcus faecalis and Enterococcus faecium. Most other species do not harbor any virulence and antibiotic resistance genes and display great potential for use as food fermentation microorganisms or as probiotics. The study contributes to the current debate on enterococci and goes against the mainstream perception of enterococci as potentially dangerous microorganisms that should not be associated with food and health.
    Keywords:  Enterococcus; antibiotic resistance genes; virulence gene; whole-genome analysis
    DOI:  https://doi.org/10.1128/aem.00415-25
  25. Gut Microbes. 2025 Dec;17(1): 2489067
      Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.
    Keywords:  Crohn’s disease; Inflammatory bowel disease; precision microbiome therapeutics; ulcerative colitis
    DOI:  https://doi.org/10.1080/19490976.2025.2489067
  26. Arch Virol. 2025 Apr 09. 170(5): 95
      Abuse of antibiotics has led to increased rates of resistance in extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and an acceleration in the emergence of drug-resistant strains, which can have serious consequences for nosocomial infections. In this study, phage MY02, which infects ESBL-producing Klebsiella pneumoniae, was isolated from sewage and characterized. Phage MY02 was found to have an optimal multiplicity of infection of 0.001, with a lysis period of up to 40 minutes and an average burst of about 80 plaque-forming units per cell. The phage was found to be stable over a temperature range of -20 to 60°C and a pH range of 3-11 and to have a broad host range. Whole-genome sequencing showed that the genome of phage MY02 is ??171,821?? bp in length and contains 293 open reading frames. Sequence comparisons and phylogenetic analysis showed that phage MY02 belongs to the genus Marfavirus in the class Caudoviricetes. This novel broad-spectrum Klebsiella pneumoniae phage has potential applications against bacterial infections.
    DOI:  https://doi.org/10.1007/s00705-025-06281-x
  27. J Clin Aesthet Dermatol. 2025 Mar-Apr;18(3-4 Suppl 1):18(3-4 Suppl 1): S16-S23
      Clinical trials are designed to evaluate the efficacy and safety of new drugs. However, greater focus is often placed on efficacy rather than safety. This review article discusses the fundamentals involved in evaluating the safety of a new drug. In addition, the principal challenges involved in the collection, analysis, reporting, and interpretation of safety data in clinical trials are described using relevant examples. These challenges include the fact that clinical trials are generally limited in size and duration, exclude high-risk populations, and have limited statistical power to detect rare but potentially serious adverse events (AEs) that might occur in real-world situations. Reporting of safety data across clinical trials is also inconsistent. A thorough understanding of the interpretation of safety data, especially the appropriate use of exposure-adjusted incidence rates (EAIRs) in relation to AEs, as well as the importance of comparing rates to those reported in the general population and in patients with psoriasis, is vital for making a well-informed assessment of the safety of a new drug. The information provided in this article could be useful to healthcare providers who must evaluate a large volume of safety data when providing evidence-based treatment suggestions and recommendations to their patients.
    Keywords:  Adverse events; exposure-adjusted incidence rates; laboratory parameters; randomized controlled trials; safety
  28. Open Vet J. 2025 Feb;15(2): 847-862
       Background: Staphylococcus aureus is a well-known opportunistic pathogen widely present in humans and food- producing animals. The emergence of antimicrobial resistance (AMR) in S. aureus represents a major challenge to animal and public health. Poor biosecurity practices and the misuse and overuse of veterinary drugs in farming settings may apply environmental pressure, which favors the selection of AMR bacteria.
    Aim: This study aimed to describe veterinary drug usage (VDU), prevalence of AMR phenotypes, and associations among S. aureus isolates from swine of smallholder farms in Central Vietnam.
    Methods: A cross-sectional survey was conducted to collect VDU data from smallholder swine farms. A total of 155 nasal swab samples were collected and used for isolating S. aureus. The AMR of S. aureus strains was tested using the disk diffusion method.
    Results: Approximately 56.8%, 71.6%, 36.1%, and 69.7% of farmers used vaccines, disinfectants, and antimicrobials (AMs) for prevention and treatment, respectively. Of the 155 nasal swab samples, 99 (63.9%) were positive for S. aureus. Resistance was most commonly observed against oxacillin (59.6%), cefotaxime (59.6%), and linezolid (53.5%). Positive associations were found between the use of vaccines and resistance to oxytetracycline (OR = 3.28, p = 0.01) and povidone usage and resistance to meropenem (OR = 9.35, p = 0.03). Almost all positive associations were observed between the use of AMs (for both prevention and treatment) and AMR in S. aureus. Negative associations were found between resistance to oxytetracycline and the use of gentamicin, linezolid, streptomycin, and norfloxacin.
    Conclusion: The present study highlights information on VDU, prevalence, AMR, and their associations with S. aureus isolated from a smallholder swine farm in Central Vietnam. These findings are expected to aid in developing countermeasures against AMR against swine production in Vietnam.
    Keywords:  Antimicrobial; Disinfectant; Resistance; Staphylococcus aureus; Swine; Vaccine
    DOI:  https://doi.org/10.5455/OVJ.2025.v15.i2.34
  29. Recenti Prog Med. 2025 Apr;116(4): 211-218
      Rhinitis is an extremely common disease, to the extent that it actually affects the entire population throughout its lifetime. Rhinitis can be classified according to the etiopathogenetic mechanisms involved. Regarding the cause, rhinitis can be infectious, allergic, non-allergic, secondary to other diseases and iatrogenic. In clinical practice, two main pathophysiological mechanisms cause an alteration in nasal physiology: nasal obstruction and mucus overproduction. Nasal obstruction can be due to two main causes, which are acute infection and allergy. Topical nasal therapy is the safest and most effective modality to rapidly achieve normal nasal patency. In particular, the paradigmatic modality of local therapy is nasal lavage, better defined as nasal irrigation. Nasal irrigation is an actual washing of the nasal cavity to remove excess mucus, inflammatory cells, mediators, cytokines, pathogens and all harmful substances. A recent Intersocietal Delphi Consensus was conducted in order to reach agreement on several aspects of topical nasal therapies. In this regard, a recent randomized controlled trial showed that a product containing PEG, bicarbonates and sodium chloride, administered to a group of patients with rhinitis or rhinosinusitis through a squeezable bottle was able to significantly reduce the intensity of symptoms and their impact on daily life. In conclusion, nasal irrigation can be considered a valid treatment option in the management of upper airway disorders. At the same time, it is important that more physicians become aware of the usefulness of this therapeutic method.
    DOI:  https://doi.org/10.1701/4480.44814