bims-fagtap 2025-04-27 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–04–27
25 papers selected by
Luca Bolliger, lxBio

The future of phage therapy in the USA.
Evaluating the safety, pharmacokinetics and efficacy of phage therapy in treating fracture-related infections with multidrug-resistant Staphylococcus aureus: intravenous versus local application in sheep.
Advancing RNA phage biology through meta-omics.
Communicating the promise of phage therapy.
Bacteriophage application in inhibiting corrosion- producing bacteria.
Isolation and Characterization of Virulent Bacteriophages and Controlling Salmonella Enteritidis Biofilms on Chicken Meat.
Bacteriophage-embedded and coated alginate layers inhibit biofilm formation by clinical strains of Klebsiella pneumoniae.
Studies in vitro e in vivo of phage therapy medical products (PTMPs) Targeting Clinical Strains of Klebsiella pneumoniae belonging to the clone ST512.
Proteomic Analysis of Marine Bacteriophages: Structural Conservation, Post-Translational Modifications, and Phage-Host Interactions.
Phage therapy: a potential breakthrough in Tuberculosis treatment.
Isolation, characterization, and application of the novel polyvalent bacteriophage vB_EcoM_XAM237 against pathogenic Escherichia coli.
Therapeutic Potential of Novel Phages with Antibiotic Combinations Against ESBL-Producing and Carbapenem-Resistant Escherichia coli.
Molecular epidemiology and emergence of sequence type 25 hypervirulent Klebsiella pneumoniae in pigs in the Netherlands (2013-2020): a global comparative analysis with human and pig isolates.
Investigating the occurrence of antimicrobial resistance in the environment in Canada: A scoping review.
Application of phage-derived enzymes for enhancing food safety.
Harnessing the Human Microbiome for Innovative Drug Delivery Systems: Exploring Pharmacomicrobiomics and Targeted Therapies.
Bacteriological Profile of Diabetic Foot Ulcer With Special Reference to Biofilm Formation.
Drug resistance phenotypes of clinical Klebsiella pneumoniae isolates in the past 20 years in China: a systematic review and meta-analysis.
Antibiotic Resistance Genes in Agricultural Soils: A Comprehensive Review of the Hidden Crisis and Exploring Control Strategies.
Role of gut microbiome in suppression of cancers.
Tracking the evolution and persistence of antibiotic resistance in the human gut.
Gut microbiota development across the lifespan: Disease links and health-promoting interventions.
Comparison of phage and plasmid populations in the gut microbiota between Parkinson's disease patients and controls.
"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".
Population and pan-genomic analyses of Staphylococcus pseudintermedius identify geographic distinctions in accessory gene content and novel loci associated with AMR.

Trends Mol Med. 2025 Apr 22. pii: S1471-4914(25)00084-X. [Epub ahead of print]

The future of phage therapy in the USA.

Brandon A Berryhill, Teresa Gil-Gil, Andrew P Smith, Bruce R Levin.

  Fueled by the increasing abundance of antibiotic-resistant pathogens, there has been a resurrection in the use of bacterial viruses (bacteriophages or 'phage') for therapeutic applications. Phage therapy was used in the early 20th century to limited success, which we attribute to its haphazard employment. To avoid repeating the mistakes of the past, this Opinion first evaluates the historical reasons for the failure of phage therapy, analyzes the current state of the field, and ultimately makes recommendations for how to proceed with contemporary phage therapy. Despite many advances in phage biology, crucial gaps in our knowledge persist. Our recommendations require physicians, scientists, and public-policy leaders to cooperate to bridge the outstanding gaps around phage therapy to develop phage into a useful therapeutic tool.

Keywords:  antibiotic resistance; bacteriophage; clinical trials; government regulation; personalized medicine; phage therapy

DOI:  https://doi.org/10.1016/j.molmed.2025.03.013
Front Cell Infect Microbiol. 2025 ;15 1547250

Evaluating the safety, pharmacokinetics and efficacy of phage therapy in treating fracture-related infections with multidrug-resistant Staphylococcus aureus: intravenous versus local application in sheep.

Christian Peez, Baixing Chen, Leopold Henssler, Marco Chittò, Jolien Onsea, Michael H J Verhofstad, Daniel Arens, Caroline Constant, Stephan Zeiter, William Obremskey, Andrej Trampuz, Michael J Raschke, Charalampos Zalavras, Willem-Jan Metsemakers, T Fintan Moriarty.

   Background: Fracture-related infections (FRI), particularly those caused by antibiotic resistant Staphylococcus aureus, present significant clinical challenges due to the formation of biofilm on the implanted device, and reduced options for conventional antibiotic treatment. Bacteriophage (phage) therapy (PT) offers a targeted approach to managing such infections, however, evidence for pharmacokinetics and optimal route of administration is limited for FRI. This study aimed to evaluate safety, phage distribution kinetics, phage neutralization, and antibacterial efficacy after intravenous or local administration in a sheep model.
Methods: The study was conducted in two phases: Phase 1 assessed the safety and distribution of two successive rounds of intravenous and local phage administration in non-infected sheep, while Phase 2 evaluated the therapeutic efficacy of intravenous versus local phage administration in combination with intravenous vancomycin in treating MRSA-induced FRI (tibial osteotomy with plate fixation). The specific pathogen and phage used in the sheep were both taken from a human FRI patient treated with PT. Phage neutralization and phage distribution were the primary outcomes measured in both phases of the sheep study.
Results: Both intravenous and local phage administration were well-tolerated in non-infected sheep. Phages were cleared rapidly from circulation after intravenous administration, with no phage detected after 240 minutes. Phage neutralization increased during PT, peaking at 99.9% in non-inoculated sheep by the end of the second phage treatment (day 50). In infected sheep, phage neutralization levels reached a maximum of 99.9% earlier (day 13), with no significant differences between intravenous and local administration. The bacterial load was not significantly changed by PT, either IV or locally applied.
Conclusions: PT is a safe adjunct to antibiotic treatment for FRI, however, phage neutralization developed rapidly and was accelerated in infected hosts. Further research is required to optimize phage selection, dosing, and delivery methods to enhance its therapeutic potential as an adjunct to conventional antibiotic therapy, particularly in the face of challenges such as rapid clearance and phage neutralization.

Keywords:  MRSA; Staphylococcus aureus; administration; bacteriophage; fracture related infection; neutralization; osteomyelitis; pharmacokinetics

DOI:  https://doi.org/10.3389/fcimb.2025.1547250
Nucleic Acids Res. 2025 Apr 22. pii: gkaf314. [Epub ahead of print]53(8):

Advancing RNA phage biology through meta-omics.

Jens Hör.

Bacteriophages with RNA genomes are among the simplest biological entities on Earth. Since their discovery in the 1960s, they have been used as important models to understand the principal processes of life, including translation and the genetic code. While RNA phages were generally thought of as rare oddities in nature, meta-omics methods are rapidly changing this simplistic view by studying diverse biomes with unprecedented resolution. Metatranscriptomics dramatically expanded the number of known RNA phages from tens to tens of thousands, revealed their widespread abundance, and discovered several new families of potential RNA phages with largely unknown hosts, biology, and environmental impact. At the same time, (meta)genomic analyses of bacterial hosts are discovering an arsenal of defense systems bacteria employ to protect themselves from predation, whose functions in immunity against RNA phages we are only beginning to understand. Here, I review how meta-omics approaches are advancing the field of RNA phage biology with a focus on the discovery of new RNA phages and how bacteria might fight them.

DOI: https://doi.org/10.1093/nar/gkaf314
Nat Microbiol. 2025 Apr 23.

Communicating the promise of phage therapy.

Sabrina Green.

DOI: https://doi.org/10.1038/s41564-025-01992-y
BMC Microbiol. 2025 Apr 23. 25(1): 241

Bacteriophage application in inhibiting corrosion- producing bacteria.

Guangming Zhang, Zisheng Guo, Shuo Liu, Qiaoli Yang, Yiming Yuan, Ke Guo, Weixiao Wang, Haina Wang, Jie Feng, Wei Chen, Yanmei Sun, Shiwei Wang.

  Sulfate-reducing bacteria (SRB) are a major cause of microbially-induced corrosion (MIC) and souring (MIS), leading to significant challenges in industries like oil recovery and wastewater treatment. Due to SRB's resistance to antimicrobial agents, bacteriophage (phage) therapy offers a promising alternative for SRB control. In this study, a novel lytic phage, SRB7757, targeting Desulfovibrio vulgaris, was isolated from sewage. SRB7757 inhibited sulfide production by 92.3% within 24 h and significantly reduced corrosion on metal specimens after 28 days, highlighting its potential in controlling MIC and MIS. Genome analysis revealed SRB7757 has a genome size of 142,573 bp, 217 ORFs, and 6 tRNAs, and belongs to the Chaseviridae family. SRB7757 exhibits a latent period of 4 h, a burst size of ~ 100 PFU/cell, and is stable between 4 °C and 60 °C across a pH range of 2.0-12.0. Two predicted lytic enzymes of SRB7757 demonstrated higher inactivation and biofilm removal rates.

Keywords:   Desulfovibrio phage; Microbially-induced corrosion; Phage anticorrosion; Sulfate-reducing bacteria

DOI:  https://doi.org/10.1186/s12866-025-03952-2
Microb Pathog. 2025 Apr 22. pii: S0882-4010(25)00344-4. [Epub ahead of print] 107619

Isolation and Characterization of Virulent Bacteriophages and Controlling Salmonella Enteritidis Biofilms on Chicken Meat.

Xiaowen Sun, Fan Xue, Cong Cong, Bilal Murtaza, Chenxi Guo, Haochen Su, Xiaoyu Li, Lili Wang, Yongping Xu.

  Salmonella is a prominent zoonotic pathogen that continues to represent a large threat to food safety and public health worldwide. Concurrently, the inappropriate use of antibiotics has led to the development of antibiotic-resistant strains of Salmonella, highlighting the urgent need for new approaches to manage these bacteria. In this context, virulent bacteriophages are increasingly recognized as a potential and effective biological control method against Salmonella. This study identifies two newly isolated virulent Salmonella phages, phage vB_SalD_ABTNLS3 (S3 for short) and phage 2-3 (2-3 for short). Both phages exhibited effectiveness in preventing biofilm formation and reducing biofilm. S3 and 2-3 could maximize the inhibition of more than 70% and 91% of biofilm formation after 48 h of treatment, and maximize the removal of more than 59 % and 96 % of mature biofilm after 3 h and 5 h, respectively. Based on these, our study assessed the efficacy of 2-3 in controlling Salmonella enterica serotype Enteritidis (SE) on raw chicken meat at 4°C with varying MOIs, including 1, 100, and 10,000. The maximum reduction observed in SE on chicken meat was 1.15 log10 CFU/mL following a 12-hour treatment with the 2-3, a significant decrease of more than 92% compared to the initial levels present in the experiment (MOI = 10,000). In conclusion, our phages performed well in controlling biofilm and disinfecting refrigerated food at 4°C, suggesting their potential as biological agents to reduce Salmonella contamination in the food industry.

Keywords:  Bacteriophage; Biofilm; Food safety; Foodborne pathogen; Salmonella Enteritidis

DOI:  https://doi.org/10.1016/j.micpath.2025.107619
J Appl Microbiol. 2025 Apr 23. pii: lxaf099. [Epub ahead of print]

Bacteriophage-embedded and coated alginate layers inhibit biofilm formation by clinical strains of Klebsiella pneumoniae.

Hala R Ali, Carlos Valdivia, David Negus.

   AIMS: This study aimed to determine the antibiofilm properties of Klebsiella pneumoniae phages previously isolated from Thai hospital sewage water. Furthermore, we aimed to develop a phage-embedded and coated alginate hydrogel, suitable as a wound dressing or surface coating to prevent K. pneumoniae proliferation and biofilm formation.
METHODS AND RESULTS: The biofilm forming capacity of six clinical K. pneumoniae isolates was determined by means of the crystal violet assay and four strains which exhibited strong adherence were selected for further characterisation. Two phages (vB_KpnA_GBH014 and vB_KpnM_GBH019) were found to both significantly prevent (P = <0.0005) and disrupt (P = <0.05) biofilms produced by their K. pneumoniae hosts as determined by optical density readings using the crystal violet assay. Furthermore, alginate layers embedded and coated with phages vB_KpnA_GBH014 and vB_KpnM_GBH019 produced antibiofilm surfaces. Viable counts of recovered biofilms showed that alginate hydrogels containing phage vB_KpnA_GBH014 or vB_KpnM_GBH019 were associated with significantly fewer K. pneumoniae versus no-phage controls (1.61×108 cfu ml-1 vs 1.67×104 cfu ml-1, P = <0.005 and 1.78×108 cfu ml-1 vs 6.11×102 cfu ml-1, P = <0.00005, respectively). Confocal microscopy further revealed a significant reduction in the biovolume of biofilms formed on phage embedded and coated alginate hydrogels compared to no-phage controls.
CONCLUSIONS: Phages vB_KpnA_GBH014 and vB_KpnM_GBH019 can both prevent and disrupt biofilms produced by clinical isolates of K. pneumoniae. Embedding and coating these phages into alginate produces an antibiofilm matrix which may have promise for coating medical devices or as a wound dressing.

Keywords:  AMR; biofouling; multidrug-resistant

DOI:  https://doi.org/10.1093/jambio/lxaf099
Antimicrob Agents Chemother. 2025 Apr 23. e0193524

Studies in vitro e in vivo of phage therapy medical products (PTMPs) Targeting Clinical Strains of Klebsiella pneumoniae belonging to the clone ST512.

Inés Bleriot, Lucía Blasco, Patricia Fernández-Grela, Laura Fernández-García, Lucia Armán, Clara Ibarguren, Concha Ortiz-Cartagena, Antonio Barrio-Pujante, José Ramón Paño, Jesús Oteo-Iglesias, María Tomás.

  The widespread incidence of antimicrobial resistance has created renewed interest in the use of alternative antimicrobial treatments such as phage therapy. Phages are viruses that infect bacteria and generally have a narrow bacteria host-range. Combining phages with antibiotics can prevent the emergence of bacterial resistance. The aim of the present study was to develop phage therapy medical products (PTMPs) targeting clinical isolates of carbapenem-producing Klebsiella pneumoniae belonging to the high-risk clone ST512. From a collection of 22 seed of lytic phages sequenced belonging to MePRAM collection (Spanish Health Precision Medicine Project against Antimicrobial Resistance), four were used to generate PTMPs (CAC_Kpn1 and CAC_Kpn2). These PTMPs were partly active against three of the clinical strains of clone ST512 (A, B, and C). The use of Appelmans method in the CAC_Kpn1_ad (adapted CAC_Kpn1) yielded a significant increase in the efficacy against strain A, while adapted CAC_Kpn2 (CAC_Kpn2_ad) only effectively reduced bacterial survival when combined with ½ × MIC ß-lactam antibiotic meropenem for 24 h in clinical strains B and C, showed after this time, resistance to PTMPs. In addition, the amounts of endotoxin released by the PTMPs were quantified and subsequently reduced in preparation for in vivo use of the PTMPs in the Galleria mellonella infection model, confirming the in vitro results from the CAC_Kpn1_ad and CAC_Kpn2_ad. To sum up, the preparation of two PTMPs and their subsequent adaptation can be a good approach to solve part of the occurrence of antimicrobial resistance. In addition, the use of the larval model is an effective method to discriminate the efficacy of in vivo treatment.

Keywords:  Galleria mellonella; Klebsiella pneumoniae; endotoxins; phage therapy medical products (PTMPs); phage-antibiotic synergy

DOI:  https://doi.org/10.1128/aac.01935-24
Environ Microbiol. 2025 Apr;27(4): e70099

Proteomic Analysis of Marine Bacteriophages: Structural Conservation, Post-Translational Modifications, and Phage-Host Interactions.

Shuzhen Wei, Anan Wang, Lanlan Cai, Ruijie Ma, Longfei Lu, Jiangtao Li, Rui Zhang.

  Marine bacteriophages, the most abundant biological entities in marine ecosystems, are essential in biogeochemical cycling. Despite extensive genomic data, many phage genes remain uncharacterised, creating a gap between genomic diversity and gene function knowledge. This gap limits our understanding of phage life cycles, assembly, and host interactions. In this study, we used mass spectrometry to profile the proteomes of 13 marine phages from diverse lifestyles and hosts. The analysis accurately annotated hypothetical genes, mapped virion protein arrangements, and revealed structural similarities among phages infecting the same host, particularly in tail fibre proteins. Protein structure comparisons showed conservation and variability in head and tail proteins, particularly in key domains involved in virion stabilisation and host recognition. For the first time, we identified post-translational modifications (PTMs) in marine phage proteins, which may enhance phage adaptability and help evade host immune systems. These findings suggest that phages optimise their infection strategies through structural variations and PTM modifications, improving their adaptability and host interactions.

Keywords:  marine viruses; phage–host interactions; post‐translational modifications; proteomic

DOI:  https://doi.org/10.1111/1462-2920.70099
J Pak Med Assoc. 2025 Apr;75(4): 678-679

Phage therapy: a potential breakthrough in Tuberculosis treatment.

Muhammad Aliyan Ahmed, Yasir Ahmad.

DOI: https://doi.org/10.47391/JPMA.21831
Vet Res. 2025 Apr 24. 56(1): 90

Isolation, characterization, and application of the novel polyvalent bacteriophage vB_EcoM_XAM237 against pathogenic Escherichia coli.

Jiyun Chai, Hongfei Sun, Stefan Schwarz, Yuxuan Huang, Shuangyu Xie, Qiu Xu, Longhua Lin, Caiping Ma, Jie Hou, Yao Zhu, Wanjiang Zhang.

  A novel polyvalent broad-spectrum phage, vB_EcoM_XAM237 (XAM237), was isolated from pig farm sewage. It can simultaneously lyse multiple strains of pathogenic Escherichia coli (E. coli), demonstrating a broad host range. When the enteropathogenic E. coli (EPEC) strain E711 was used as the host bacterium, the phage XAM237 exhibited a short latent period, high stability at different temperatures and pH values and good tolerance to chloroform. Moreover, phage XAM237 can efficiently adsorb and lyse host bacteria in vitro. Whole-genome sequencing revealed that XAM237 is a double-stranded DNA (dsDNA) phage consisting of 170 541 bp with a G + C content of 35%. Phylogenetic analysis confirmed that XAM237 belongs to the family Straboviridae, genus Tequatrovirus. In addition, the genome of XAM237 did not contain genes related to lysogenicity, virulence or antimicrobial resistance. The effects of phage XAM237 in treating EPEC infections in vivo were evaluated in a mouse model. Phage XAM237 was able to reduce the number of colonized aEPEC strain E711 in the small intestine, liver, spleen, and kidney. This study suggested that phage XAM237 may be a promising candidate biologic agent for controlling pathogenic E. coli infections.

Keywords:  Bacteriophage; biological characteristics; genome analysis; pathogenic Escherichia coli ; phage therapy

DOI:  https://doi.org/10.1186/s13567-025-01514-y
J Glob Antimicrob Resist. 2025 Apr 21. pii: S2213-7165(25)00077-3. [Epub ahead of print]

Therapeutic Potential of Novel Phages with Antibiotic Combinations Against ESBL-Producing and Carbapenem-Resistant Escherichia coli.

Md Shamsuzzaman, Shukho Kim, Jungmin Kim.

   OBJECTIVES: The emergence of extended-spectrum β-lactamase (ESBL)-producing E. coli and carbapenem-resistant E. coli (CREC) is a significant global health challenge. This study focuses on isolating and characterizing two novel phages, EC.W1-9 and EC.W15-4, and investigating their efficacy with antibiotics against these resistant E. coli.
METHODS: In vivo experiments were conducted using BALB/c mice, and E.coli isolates were collected, cultured, and evaluated for antibiotic susceptibility. Phages were isolated from hospital sewage and prepared to infect the E. coli.
RESULTS: The isolated phages, EC.W1-9 and EC.W15-4, belonged to the Podoviridae and Straboviridae families, and lack integrase or toxin-coding genes, indicating safety for therapeutic use. The combination of these phages significently enhanced their lytic ability, lysing 61.7% of 60 E. coli isolates, compared to 41.6%-55% lysis by individual phages. Furthermore, the phage combination demonstrated 100% susceptibility against different E. coli sequence types, including ST73, ST648, ST2311, ST405, ST7962, ST131, ST13003, and ST167. Additionally, synergy between antibiotics and phage combinations improved susceptibility rates to 73.3% for ESBL producers and 54% for CREC. The combined treatment of isolated phages and antibiotics significantly increased survival rates in BALB/c mice exposed to resistant STs of E.coli, including ST131, ST648, and ST410. Survival rates against ST131 increased by approximately 75% and 50% compared to treatment individual phages. Combined treatment with two phages and antibiotics resulted in 75-100% survival against E. coli ST410 and 100% survival against ST648 CONCLUSIONS: This study highlights the therapeutic importance of phage and phage-antibiotic combinations in combating ESBL-producing E. coli and CREC isolates.

Keywords:  ESBL-producing and CR E. coli; phage combination; phage-antibiotic synergism; sequence type; therapeutic efficiency

DOI:  https://doi.org/10.1016/j.jgar.2025.04.005
Microb Genom. 2025 Apr;11(4):

Molecular epidemiology and emergence of sequence type 25 hypervirulent Klebsiella pneumoniae in pigs in the Netherlands (2013-2020): a global comparative analysis with human and pig isolates.

Soe Yu Naing, Aldert Zomer, Linda van der Graaf-van Bloois, Manon Houben, Karin Junker, Otto Schreurs, Annet Heuvelink, Jaap A Wagenaar, Jobke van Hout.

  Klebsiella pneumoniae (Kp), a ubiquitous pathogen found in diverse ecological niches, poses a threat to human and animal health. Hypervirulent Kp (hvKp) is concerning for its acquisition of virulence and antimicrobial resistance genes through plasmids. This study investigates hvKp as a cause of septicaemia in piglets in the Netherlands and examines the role of plasmids in virulence and host association. We collected 41 Kp isolates cultured from necropsies submitted from 15 different farms (2013-2020) and sequenced them using long-read sequencing. We identified sequence type (ST) 25 as the dominant Kp (67%, 10/15 farms) associated with septicaemia in pigs in the Netherlands. ST25 isolates displayed a hypervirulent profile, including the K2 hyper-capsule type and carried an iuc3 virulence plasmid. Further analysis revealed two ST25 clonal groups: CG25 and CG3804, a novel porcine clone. Multidrug resistance was identified in CG25 isolates from five pig farms. There was one colistin-resistant isolate carrying mcr-1 on a plasmid. Comparative genomic analysis was performed by including a large dataset of related publicly available Kp genomes from ST25 humans (n=230) and pigs (n=12) of all STs for phylogenetic and plasmid analysis. Pangenomic analysis revealed significantly higher iuc3 prevalence in global CG25 pig isolates (98%, 40/41) compared to humans (10%, 24/234) correlating with their enhanced virulence (scores 3-4 vs 0-1). The study highlights ST25 hvKp causing septicaemia in piglets in the Netherlands for the first time. Aerobactin lineage iuc3 on a plasmid is associated with infections in pigs and is responsible for an increased virulence score.

Keywords:  aerobactin plasmid; antimicrobial resistance; emerging infectious diseases; hypervirulent Klebsiella pneumoniae; iuc3; septicaemia; whole-genome sequencing

DOI:  https://doi.org/10.1099/mgen.0.001388
Can J Microbiol. 2025 Apr 25.

Investigating the occurrence of antimicrobial resistance in the environment in Canada: A scoping review.

Manuel Alejandro Pérez Maldonado, Daniel Ofori-Darko, Vanessa Nichols, Jessica French, Kelsey Spence, Richard Reid-Smith, Jane Parmley.

Antimicrobial resistance is an environmental, agricultural, and public health problem that is impacting the health of humans and animals. The role of the environment as a source of and transmission pathway for antibiotic resistant bacteria and antibiotic resistance genes is a topic of increasing interest that, to date, has received limited attention. This study aimed to describe the sources and possible pathways contributing to antimicrobial resistance dissemination through bioaerosols, water, and soil in Canada using a scoping review methodology and systems thinking approach. A systems map was created to describe the occurrence and relationships between sources and pathways for antimicrobial resistance dissemination through water, soil, and bioaerosols. The map guided development of the scoping review protocol, specifically the keywords searched and what data were extracted from the included studies. In total, 103 studies of antimicrobial resistance in water, 67 in soil and 12 in air were identified. Studies to detect the presence of antimicrobial resistance genes have mainly been conducted at wastewater treatment plants and commercial animal livestock facilities. We also identified elements in the systems map with little or no data available (e.g., retail) that need to be investigated further to have a better understanding of antimicrobial resistance dissemination through different Canadian environments.

DOI: https://doi.org/10.1139/cjm-2024-0189
Food Res Int. 2025 May;pii: S0963-9969(25)00655-6. [Epub ahead of print]209 116318

Application of phage-derived enzymes for enhancing food safety.

Junhwan Kim, Xinyu Liao, Song Zhang, Tian Ding, Juhee Ahn.

  Foodborne pathogens such as Salmonella, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus present significant public health threats, causing widespread illness and economic loss. Contaminated food is responsible for an estimated 600 million illnesses and 420,000 deaths annually, with low- and middle-income countries facing losses of approximately $110 billion each year. Traditional methods to ensure food safety, including antimicrobials and preservatives, can contribute to the development of antimicrobial-resistant bacteria, highlighting the need for alternative strategies. Bacteriophages are gaining renewed attention as promising alternatives to conventional antibiotics due to their specifically target bacteria and their lower potential for causing adverse effects. However, their practical application is limited by challenges such as narrow host ranges, the emergence of phage-resistant bacteria, and stability issues. Recent research has shifted focus towards phage-derived enzymes, including endolysins, depolymerases, holins, and spanins, which are involved in the phage lytic cycle. These enzymes, as potential approaches to food safety, have demonstrated significant efficacy in targeting and lysing bacterial pathogens, making them suitable for controlling foodborne pathogens and preventing foodborne illnesses. Phage-derived enzymes also show promise in controlling biofilms and enhancing antimicrobial activity when combined with other antimicrobials. Therefore, this review emphasizes recent advancements in the use of the phage-derived enzymes for food safety, addresses their limitations, and suggests strategies to enhance their effectiveness in food processing and storage environments.

Keywords:  Antimicrobial resistance; Bacteriophage; Biofilm control; Endolysin; Food safety; Phage-derived enzyme

DOI:  https://doi.org/10.1016/j.foodres.2025.116318
Curr Pharm Des. 2025 Apr 21.

Harnessing the Human Microbiome for Innovative Drug Delivery Systems: Exploring Pharmacomicrobiomics and Targeted Therapies.

Manisha S Jain, Samathoti Prasanthi, Nirmala Devi Bommala, Prakash Goudanavar, N Raghavendra Naveen.

  The human gut microbiome has emerged as a crucial component of health and disease, presenting novel opportunities for the development of drug delivery systems based on microbiome interactions. This paper explores advanced strategies utilizing microorganisms, engineered bacteria, viruses, and bacteria-encapsulated nanoparticles as next-generation therapeutic vehicles. Focusing on analytical approaches to phage therapy and bio-hybrid bacteria for targeted drug delivery, the article highlights recent breakthroughs in colon-specific targeting for gastrointestinal disorders. The study also delves into the emerging field of pharmacomicrobiomics, with an emphasis on applications in cancer, cardiovascular, digestive, and nervous system treatments, specifically targeting key drug classes such as ACE inhibitors, proton-pump inhibitors, and NSAIDs. Challenges related to cytotoxicity and toxicity are addressed, offering proposals for safer therapeutic applications. This review underscores the transformative potential of the microbiome in personalized medicine and targeted drug delivery, with a focus on its integration with advanced technologies to optimize therapeutic outcomes.

Keywords:  Human gut microbiome; bacteria-encapsulated nanoparticles; drug delivery systems; microbiome engineering.; microbiome-targeted therapy; pharmacomicrobiomics; proteinaceous drugs; reactive oxygen species; synthetic biology; virus-based drug delivery

DOI:  https://doi.org/10.2174/0113816128354250250326045943
Cureus. 2025 Mar;17(3): e80974

Bacteriological Profile of Diabetic Foot Ulcer With Special Reference to Biofilm Formation.

Nitya Tirumala, Leela Rani K.

  Introduction Diabetes mellitus is a metabolic disorder characterized by abnormally high sugar levels in the blood for prolonged periods of time. The world's largest number of diabetics resides in India, making it the world's diabetic capital, with a diabetic foot ulcer (DFU) incidence of around 8-17%. Due to the polymicrobial and multidrug resistant (MDR) nature of DFUs, antimicrobial susceptibility testing is of high importance to help treat patients effectively and prevent the development of MDR bacteria. The ability to form biofilms is a significant additive to virulence of an organism that causes an able strain to be resistant to more antibiotics as compared to a free-living strain, thereby further delaying the healing of DFUs. Materials and methods This study included 74 samples collected from patients with DFUs, out of which 69 (93.24%) yielded growth on culture. Gram staining was done for the direct microscopy, isolation, and determination of organism, and the detection of biofilm formers using Congo Red Agar plates. Data were tabulated and statistically analyzed. Results Out of 74 samples collected, 69 (93.24%) yielded growth on culturing, with 5 (6.76%) cultures coming back negative. On Gram staining, 42 (56.8%) samples showed Gram-positive cocci and 53 (71.6%) showed Gram-negative bacilli. On isolating organisms from the samples, 16 (21.7%) samples had Pseudomonas aeruginosa, followed by Klebsiella pneumoniae at 13 (17.6%) and Proteus mirabilis and Escherichia coli at 11 each (14.9%), indicating a Gram-negative bacteria predominance. Of the Gram-positive bacteria isolated, Staphylococcus aureus stands at two (2.7%) and Streptococcus pyogenes at one (1.4%). The prevailing monomicrobiality could be attributed to antibiotic administration prior to sample collection. On antibiotic sensitivity of organisms tested against each antibiotic, more than 75% of tested samples were resistant to ampicillin, cefuroxime, and erythromycin, and around 70% and more of tested samples were sensitive to ertapenem, meropenem, amikacin, gentamicin, benzylpenicillin, vancomycin, and clindamycin. Out of the 69 positive cultures, 29 (42.03%) yielded biofilm formers. Pseudomonas aeruginosa was the predominant biofilm former with 10 (34.48%) of 29 of total biofilm-forming isolates, followed by E. coli and K. pneumoniae with five each (17.24%) and Proteus mirabilis with three samples (10.34%). Regarding strains forming biofilms according to bacterium species, S. aureus was predominant, with 100% (two out of two samples) of isolates forming biofilms. Staphylococcus aureus was followed by Pseudomonas aeruginosa with 62.5% (10 out of 16 samples), Acinetobacter baumannii (two out of four samples) and Enterobacter cloacae (one out of two samples) with 50% each, E. coli with 45.45% (5 out of 11 samples), and K. pneumoniae with 38.46% (5 out of 13 samples) of isolates forming biofilms. It should be noted that only two S. aureus, four A. baumannii, and two Enterobacter cloacae samples were isolated in comparison to a larger number of Gram-negative bacteria. This study has found that 100% of multidrug-resistant organisms (MDROs) are biofilm formers. Conclusion The ability to form biofilms adds immensely to the virulence and antibiotic resistance. Detection of biofilm formers is non-invasive and convenient to measure and would help provide insight into antibiotics to be administered to the patient, thereby reducing development of MDROs and reducing healing time.

Keywords:  antibiotic resistance (abr); bacteriological profile; biofilm formation; diabetic foot ulcer (dfu); multidrug-resistant organisms

DOI:  https://doi.org/10.7759/cureus.80974
Int J Antimicrob Agents. 2025 Apr 19. pii: S0924-8579(25)00077-9. [Epub ahead of print] 107520

Drug resistance phenotypes of clinical Klebsiella pneumoniae isolates in the past 20 years in China: a systematic review and meta-analysis.

Wei Wei, Yueran Lian, Yao Peng, Biao Kan, Zhenpeng Li, Xin Lu.

   OBJECTIVES: Monitoring the drug resistance phenotypes of Klebsiella pneumoniae is crucial in clinical practice. This study aims to evaluate the prevalence of drug-resistant of clinical K. pneumoniae isolates in China over the past two decades using a systematic review and meta-analysis.
METHODS: We systematically searched five databases for relevant articles published between January 1, 2003 and November 21, 2023. We assessed resistance of clinical K. pneumoniae strains isolated in China over the past 20 years to 15 antibiotics, which were divided into three subgroups.
RESULTS: A total of 177 studies derived from 160 articles were eligible for meta-analysis. The pooled antibiotic resistance rate ranged from 5.01% (for imipenem) to 96.03% (for ampicillin). The pooled rate of resistance to the carbapenem antibiotics imipenem and meropenem was relatively low, and subgroup analyses showed that these rates increased over time. The antibiotic resistance rate showed a geographic trend, being highest in central China and lowest in northwest China. The drug resistance rate was highest in strains isolated in specimens from patients with urinary tract infections.
CONCLUSION: This meta-analysis provides reliable data on the rate of antibiotic resistance of K. pneumoniae grouped according to isolation region, time, and source, which may be helpful for selection of antibiotics for clinical treatment. Areas requiring specific attention include management of the use of carbapenem, improving the prevention and treatment of K. pneumoniae in patients with urinary tract infections, and control of transmission of strains from one region to another.

Keywords:  Antibiotic resistance; Drug resistance; Klebsiella pneumoniae; Meta-analysis

DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107520
Toxics. 2025 Mar 24. pii: 239. [Epub ahead of print]13(4):

Antibiotic Resistance Genes in Agricultural Soils: A Comprehensive Review of the Hidden Crisis and Exploring Control Strategies.

Yuanye Zeng, Runqiu Feng, Chengcheng Huang, Jie Liu, Fengxia Yang.

  This paper aims to review the sources, occurrence patterns, and potential risks of antibiotic resistance genes (ARGs) in agricultural soils and discuss strategies for their reduction. The pervasive utilization of antibiotics has led to the accumulation of ARGs in the soil. ARGs can be transferred among microorganisms via horizontal gene transfer, thereby increasing the likelihood of resistance dissemination and heightening the threat to public health. In this study, we propose that physical, chemical, and bioremediation approaches, namely electrokinetic remediation, advanced oxidation, and biochar application, can effectively decrease the abundance of ARGs in the soil. This study also highlights the significance of various control measures, such as establishing a strict regulatory mechanism for veterinary drugs, setting standards for the control of ARGs in organic fertilizers, and conducting technical guidance and on-farm soil monitoring to reduce the environmental spread of ARGs and protect public health.

Keywords:  agricultural soil; antibiotic resistance genes; control strategies; potential risks; sources

DOI:  https://doi.org/10.3390/toxics13040239
Gut Microbes. 2025 Dec;17(1): 2495183

Role of gut microbiome in suppression of cancers.

Yao Xu, Zhaoyu Gao, Jiaying Liu, Qianqian Yang, Shunjiang Xu.

  The pathogenesis of cancer is closely related to the disruption of homeostasis in the human body. The gut microbiome plays crucial roles in maintaining the homeostasis of its host throughout lifespan. In recent years, a large number of studies have shown that dysbiosis of the gut microbiome is involved in the entire process of cancer initiation, development, and prognosis by influencing the host immune system and metabolism. Some specific intestinal bacteria promote the occurrence and development of cancers under certain conditions. Conversely, some other specific intestinal bacteria suppress the oncogenesis and progression of cancers, including inhibiting the occurrence of cancers, delaying the progression of cancers and boosting the therapeutic effect on cancers. The promoting effects of the gut microbiome on cancers have been comprehensively discussed in the previous review. This article will review the latest advances in the roles and mechanisms of gut microbiome in cancer suppression, providing a new perspective for developing strategies of cancer prevention and treatment.

Keywords:  Gut microbiome; cancer; suppression

DOI:  https://doi.org/10.1080/19490976.2025.2495183
Nature. 2025 Apr 23.

Tracking the evolution and persistence of antibiotic resistance in the human gut.



Keywords:  Antibiotics; Bioinformatics; Computational biology and bioinformatics; Genomics; Health care

DOI:  https://doi.org/10.1038/d41586-025-01161-5
J Intern Med. 2025 Apr 24.

Gut microbiota development across the lifespan: Disease links and health-promoting interventions.

Ida Schoultz, Marcus J Claesson, Maria Gloria Dominguez-Bello, Frida Fåk Hållenius, Peter Konturek, Katri Korpela, Martin Frederik Laursen, John Penders, H Roager, Tommi Vatanen, Lena Öhman, Maria C Jenmalm.

  The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.

Keywords:  adulthood; aging; gut microbiota; infancy; inflammatory diseases; intervention

DOI:  https://doi.org/10.1111/joim.20089
Sci Rep. 2025 Apr 21. 15(1): 13723

Comparison of phage and plasmid populations in the gut microbiota between Parkinson's disease patients and controls.

Ilhan Cem Duru, Alexandre Lecomte, Pia Laine, Tânia Keiko Shishido, Joni Suppula, Lars Paulin, Filip Scheperjans, Pedro A B Pereira, Petri Auvinen.

  The aging population worldwide is on the rise, leading to a higher number of Parkinson's disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We identified over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and controls (n = 68). Significant associations emerged between groups (control vs PD) based on plasmid alpha and beta diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. We also developed a predictive machine learning model based on phage abundance data, achieving a mean Area Under the Curve (AUC) of 0.74 with a standard deviation of 0.105 and a mean F1 score of 0.68 with a standard deviation of 0.14 across cross-validation folds, indicating moderate discriminatory power. Additionally, when tested on external data, the model yielded an AUC of 0.74 and an F1 score of 0.8, further demonstrating the predictive potential of phage populations in Parkinson's disease. Further, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes.

Keywords:  Gut microbiota; Mobile genetic elements; Parkinson’s disease

DOI:  https://doi.org/10.1038/s41598-025-96924-5
Curr Hypertens Rep. 2025 Apr 22. 27(1): 14

"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".

Elsayed M Mahgoup.

   PURPOSE OF REVIEW: Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.
RECENT FINDINGS: Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.

Keywords:  Blood pressure; Cardiovascular health; Clinical challenges; Gut microbiota; Hypertension; Non-pharmacological management; Probiotics

DOI:  https://doi.org/10.1007/s11906-025-01331-w
Appl Environ Microbiol. 2025 Apr 24. e0001025

Population and pan-genomic analyses of Staphylococcus pseudintermedius identify geographic distinctions in accessory gene content and novel loci associated with AMR.

Jordan D Zehr, Qi Sun, Kristina Ceres, Amy Merrill, Gregory H Tyson, Olgica Ceric, Jake Guag, Sarah Pauley, Holly C McQueary, Kelly Sams, Guillaume Reboul, Patrick K Mitchell, Renee Anderson, Rebecca Franklin-Guild, Cassandra Guarino, Brittany D Cronk, Claire R Burbick, Rebecca Wolking, Laura Peak, Yan Zhang, Rebeccah McDowall, Aparna Krishnamurthy, Durda Slavic, Prabhjot Kaur Sekhon, David Needle, Robert Gibson, Casey Cazer, Jennifer Rodriguez, Beth Harris, Michael J Stanhope, Laura B Goodman.

  Staphylococcus pseudintermedius is a common representative of the normal skin microbiota of dogs and cats but is also a causative agent of a variety of infections. Although primarily a canine/feline bacterium, recent studies suggest an expanded host range including humans. This paper details population genomic analyses of the largest yet assembled and sequenced collection of S. pseudintermedius isolates from across the USA and Canada and assesses these isolates within a larger global population genetic context. We then employ a pan-genome-wide association study analysis of over 1,700 S. pseudintermedius isolates from sick dogs and cats, covering the period 2017-2020, correlating loci at a genome-wide level, with in vitro susceptibility data for 23 different antibiotics. We find no evidence from either core genome phylogenies or accessory genome content for separate lineages colonizing cats or dogs. Some core genome geographic clustering was evident on a global scale, and accessory gene content was noticeably different between various regions, some of which could be linked to known antimicrobial resistance (AMR) loci for certain classes of antibiotics (e.g., aminoglycosides). Analysis of genes correlated with AMR was divided into different categories, depending on whether they were known resistance mechanisms, on a plasmid, or a putatively novel resistance mechanism on the chromosome. We discuss several novel chromosomal candidates for follow-up laboratory experimentation, including, for example, a bacteriocin (subtilosin), for which the same protein from Bacillus subtilis has been shown to be active against Staphylococcus aureus infections, and for which the operon, present in closely related Staphylococcus species, is absent in S. aureus.IMPORTANCEStaphylococcus pseudintermedius is an important causative agent of a variety of canine and feline infections, with recent studies suggesting an expanded host range, including humans. This paper presents global population genomic data and analysis of the largest set yet sequenced for this organism, covering the USA and Canada as well as more globally. It also presents analysis of in vitro antibiotic susceptibility testing results for the North American (NA) isolates, as well as genetic analysis for the global set. We conduct a pan-genome-wide association study analysis of over 1,700 S. pseudintermedius isolates from sick dogs and cats from NA to correlate loci at a genome-wide level with the in vitro susceptibility data for 23 different antibiotics. We discuss several chromosomal loci arising from this analysis for follow-up laboratory experimentation. This study should provide insight regarding the development of novel molecular treatments for an organism of both veterinary and, increasingly, human medical concern.

Keywords:  Staphylococcus pseudintermedius; antibiotic resistance

DOI:  https://doi.org/10.1128/aem.00010-25