bims-fagtap 2025-04-20 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–04–20
23 papers selected by
Luca Bolliger, lxBio

Bacteriophage therapy: a possible alternative therapy against antibiotic-resistant strains of Klebsiella pneumoniae.
Bypassing Evolution of Bacterial Resistance to Phages: The Example of Hyper-Aggressive Phage 0524phi7-1.
Comparative evaluation of long-term preservation methods for morphologically distinct bacteriophages.
Insertion sequence-mediated phage resistance contributes to attenuated colonization of cytolytic Enterococcus faecalis variants in the gut.
The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.
Characterization and therapeutic potential of phage vB_Eco_ZCEC08 against multidrug-resistant uropathogenic Escherichia coli.
Isolation and Characterization of a Novel Lytic Phage N22 and Its Effect on Drug-Resistant Klebsiella Pneumoniae.
Trial design of bacteriophage therapy for nontuberculous mycobacteria pulmonary disease in cystic fibrosis: The POSTSTAMP study.
Rapid formulation of a genetically diverse phage cocktail targeting uropathogenic Escherichia coli infections using the UTI89 model.
The role of bacteriophage in inflammatory bowel disease and its therapeutic potential.
Characterization and genome analysis of the novel virulent Burkholderia phage Bm1, which is active against pan-drug-resistant Burkholderia multivorans.
Diversity, structure-function relationships and evolution of cell wall-binding domains of staphylococcal phage endolysins.
A Review of Non-Thermal Interventions in Food Processing Technologies.
A Review on Rare and Symbiotic Actinobacteria: Emerging Biotechnological Tools Against Antimicrobial Resistance.
Off-Label Treatment in Inflammatory Skin Diseases-European Point of View.
The Interplay Between Nutrition and Microbiota and the Role of Probiotics and Symbiotics in Pediatric Infectious Diseases.
Insights from Shigella bacteriophage genomes analysis.
Targeting breast cancer: the promise of phage-based nanomedicines.
Isolation and genomic characterization of Psychrobacillus isolate L3 and bacteriophage Spoks: a new phage-host pair from Antarctic soil.
The human phageome: niche-specific distribution of bacteriophages and their clinical implications.
Weberviruses are gut-associated phages that infect Klebsiella spp.
A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites.
Acinetobacter baumannii: A Comprehensive Review of Global Epidemiology, Clinical Implications, Host Interactions, Mechanisms of Antimicrobial Resistance and Mitigation Strategies.

Front Microbiol. 2025 ;16 1443430

Bacteriophage therapy: a possible alternative therapy against antibiotic-resistant strains of Klebsiella pneumoniae.

Sadia Abbas, Rabia Kanwar, Kaleem Ullah, Rimsha Kanwal, Mamoon Tajamal, Muhammad Aamir Aslam, Abid Ahmad, Abdul Qadeer, Hsun-Yu Huang, Chien-Chin Chen.

  Klebsiella pneumoniae is a notorious, Gram-negative pathogen and is a leading cause of healthcare settings and community-acquired infections. This is the commensal of human microbiota and can invade and cause infections in different body parts. The global emergence of antibiotic resistance in K. pneumoniae has become a major challenge in the whole medical community. Alternative paths to treat the infections caused by these MDR pathogens are needed as these bacteria become resistant to last-resort antibiotics like colistin. The lytic bacteriophages (phages) are the bacteria's natural predators and can rapidly eliminate the bacterial cells. Phages are abundant in nature and have recently been found to be effective tools in modern biotechnology. They can be used to control the bacterial infectious diseases. They can be manipulated easily and potentially used in therapeutics, biotechnology, and research. Several studies, both in vitro and in vivo, have demonstrated the possible applications of the lytic phages in treating K. pneumoniae superbug strains. Phage endolysins have drawn the scientific world's attention because of their involvement in phage adsorption and bacterial capsules digestion. These phage-encoded enzymes digest the polysaccharide components of bacterial cell walls by recognizing and binding them. Phage lysins, being strong biological agents, are capable of effectively and swiftly eliminating bacteria. This review summarizes the information on phages of K. pneumoniae and phage-based therapies to target their bacterial hosts.

Keywords:  K. pneumoniae; antibiotic resistance; bacteriophages; endolysins; phage therapy

DOI:  https://doi.org/10.3389/fmicb.2025.1443430
Int J Mol Sci. 2025 Mar 23. pii: 2914. [Epub ahead of print]26(7):

Bypassing Evolution of Bacterial Resistance to Phages: The Example of Hyper-Aggressive Phage 0524phi7-1.

Maria Rojero, Meagan Weaver-Rosen, Philip Serwer.

  The ideal bacteriophages (phages) for the treatment of bacterial disease (phage therapy) would bypass bacterial evolution to phage resistance. However, this feature (called a hyper-aggression feature) has never been observed to our knowledge. Here, we microbiologically characterize, fractionate, genomically classify, and perform electron microscopy of the newly isolated Bacillus thuringiensis phage 0524phi7-1, which we find to have this hyper-aggression feature. Even visible bacterial colonies are cleared. Phage 0524phi7-1 also has three other features classified under hyper-aggression (four-feature-hyper-aggressive phage). (1) Phage 0524phi7-1 forms plaques that, although sometimes beginning as semi-turbid, eventually clear. (2) Clear plaques continue to enlarge for days. No phage-resistant bacteria are detected in cleared zones. (3) Plaques sometimes have smaller satellite plaques, even in gels so concentrated that the implied satellite-generating phage motion is not bacterial host generated. In addition, electron microscopy reveals that phage 0524phi7-1 (1) is a myophage with an isometric, 91 nm-head (diameter) and 210 nm-long contractile tail, and (2) undergoes extensive aggregation, which inhibits typical studies of phage physiology. The genome is linear double-stranded DNA, which, by sequencing, is 157.103 Kb long: family, Herelleviridae; genus, tsarbombavirus. The data suggest the hypothesis that phage 0524phi7-1 undergoes both swimming and hibernation. Techniques are implied for isolating better phages for phage therapy.

Keywords:  bacteriophage, aggregation of; bacteriophage, hibernation and swimming of; bacteriophage, plaque morphology of; bacteriophage, screening of; electron microscopy; ultracentrifugation

DOI:  https://doi.org/10.3390/ijms26072914
Microbiol Spectr. 2025 Apr 16. e0144224

Comparative evaluation of long-term preservation methods for morphologically distinct bacteriophages.

Wanqi Huang, Mohammadali Khan Mirzaei, Li Deng.

  The rapid increase in antibiotic resistance has led to a renewed interest in phage therapy, which has created a need for the establishment of phage collections in order to preserve diverse phages and to reduce the delivery time to patients. However, there are currently no standard methods for the long-term preservation of phages. We assessed the stability of four different phages under distinct storage conditions, including different temperatures, storage solutions, concentrations, and with or without cryoprotectant. We found that the type of storage buffer has a significant impact on phage stability, followed by the storage temperature. Phages demonstrated higher viability in lysogeny broth (LB) than saline-magnesium (SM) buffer without gelatin. We also observed a higher sensitivity to freezing in tailed phages with longer tails, such as T4. Ultimately, we found that all four phages maintained high stability after snap freezing, followed by storage at -80°C using LB as a storage buffer without cryoprotectant.
IMPORTANCE: Phage therapy, which involves treating bacterial infections using bacteriophages (phage), has shown promise as an alternative to antibiotics and can offer a solution for treating infections caused by antibiotic-resistant bacteria. However, phages are not conventional drugs and can lose their viability when stored under unsuitable conditions. Their high diversity makes finding a standard storage method for long-term preservation challenging. Here, we studied the stability of phages under different storage conditions and identified key factors affecting their viability. We have also identified a specific storage condition that can effectively preserve a wide range of phage morphotypes for over 2 years.

Keywords:  bacteriophage therapy; bacteriophages; biopreservation; phage preservation

DOI:  https://doi.org/10.1128/spectrum.01442-24
Microbiol Spectr. 2025 Apr 15. e0330324

Insertion sequence-mediated phage resistance contributes to attenuated colonization of cytolytic Enterococcus faecalis variants in the gut.

Jumpei Fujiki, Tomohiro Nakamura, Henriette Kreimeyer, Cristina Llorente, Derrick E Fouts, Bernd Schnabl.

  Specific elimination of cytolytic Enterococcus faecalis from the intestinal microbiota by bacteriophages (phages) attenuates ethanol-induced liver disease in pre-clinical studies; however, other clinical phage therapy studies have reported the occurrence of phage-resistant variants. Here, we assessed phage resistance using a cytolytic E. faecalis clinical isolate, EF01. After infecting EF01 with ΦEf2.1 (Myoviridae) or ΦEf2.2 (Podoviridae), four host variants (R-EF01ΦEf2.1-A and R-EF01ΦEf2.1-B from infection with ΦEf2.1, and R-EF01ΦEf2.2-A and R-EF01ΦEf2.2-B from infection with ΦEf2.2) were isolated. Although isolate R-EF01ΦEf2.2 exhibited resistance to both phages, isolate R-EF01ΦEf2.1 demonstrated partial resistance only to ΦEf2.1. Whole-genome sequencing of these four isolates revealed an insertion sequence, IS256, -mediated disruption of xylA in R-EF01ΦEf2.1-A and R-EF01ΦEf2.1-B. In addition, a non-synonymous mutation in epaR, essential for the complete Enterococcus polysaccharide antigen (Epa), was identified in the R-EF01ΦEf2.2-A isolate. Furthermore, R-EF01ΦEf2.2 isolates exhibited IS256-associated chromosomal deletions and lacked galE, a gene involved in Epa biosynthesis. After gavaging mice with EF01 WT, R-EF01ΦEf2.1-A, R-EF01ΦEf2.2-A, and R-EF01ΦEf2.2-B isolates, colonization of R-EF01ΦEf2.2 isolates was significantly attenuated. R-EF01ΦEf2.2 isolates exhibited less resistance to the bile salt sodium deoxycholate and showed reduced adherence to intestinal cell monolayers, suggesting that phage-resistant variants with alterations in bacterial surface molecules, potentially including those involved in Epa biosynthesis, reduced pathogen fitness by attenuating gut colonization. In summary, IS256 is involved in phage resistance of a cytolytic E. faecalis clinical isolate, and certain phage resistance mechanisms could contribute to favorable clinical outcomes by promoting the swift elimination of phage-resistant variants in the treatment of alcohol-associated hepatitis.
IMPORTANCE: Phage therapy is a promising approach for precise editing of the gut microbiota. Notably, the specific elimination of cytolytic E. faecalis from the intestinal microbiota by phages attenuates ethanol-induced liver disease in pre-clinical studies. Despite the great promise of phage therapy, the occurrence of phage-resistant variants represents a concern for the successful development of phage-based therapies. In this context, we assessed phage resistance using a cytolytic E. faecalis clinical isolate. Isolated phage-resistant variants acquired mutations or deletions of Epa biosynthesis-related genes and exhibited attenuated colonization in the gut. These phage-resistant variants showed less resistance to bile salts and reduced adherence to intestinal cell monolayers. These results suggest that even if phage-resistant variants arise during phage therapy, certain mechanisms of phage resistance may contribute to the rapid elimination of phage-resistant variants promoting favorable clinical outcomes in the treatment of alcohol-associated hepatitis.

Keywords:  bacteriophage; cytolysin; fitness cost; gut-liver axis; microbiome editing; phage therapy; trade-off

DOI:  https://doi.org/10.1128/spectrum.03303-24
Int J Mol Sci. 2025 Mar 22. pii: 2882. [Epub ahead of print]26(7):

The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Diren Beyoğlu, Jeffrey R Idle.

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.

Keywords:  MASLD; bacteriophages; bile acids; dysbiosis; endolysins; histidine; holins; intermittent fasting; microbiota; phage therapy; probiotics; tryptophan

DOI:  https://doi.org/10.3390/ijms26072882
BMC Microbiol. 2025 Apr 16. 25(1): 221

Characterization and therapeutic potential of phage vB_Eco_ZCEC08 against multidrug-resistant uropathogenic Escherichia coli.

Assmaa H Hussein, Salsabil Makky, Raghda Hager, Ian F Connerton, Ayman El-Shibiny.

   BACKGROUND: Urinary tract infections (UTIs) caused by antibiotic-resistant bacteria have become a significant public health concern. The increasing ineffectiveness of antibiotics has led to a renewed focus on investigating other strategies, such as bacteriophages, to target specific pathogenic bacteria and prevent future resistance.
RESULTS: This study reports the isolation and characterization of bacteriophage vB_Eco_ZCEC08 targeting uropathogenic Escherichia coli (UPEC). Phage vB_Eco_ZCEC08 is morphologically a non-contractile tailed phage that exhibits strong lytic activity against UPEC with a short latent period of less than 15 min and a lysis time of 20 min to produce a high burst of around 900 phage particles per host cell. vB_Eco_ZCEC08 phage activity demonstrated exceptional stability against temperature [-80-60 ̊C], pH [2-11], UV exposure and incubation in artificial human urine. The phage effectively reduced UPEC counts over a range of infection rates, with MOI 1 the most effective, and which resulted in the limited emergence of phage-insensitive bacteria. A whole-genome study of the 47.926 bp vB_Eco_ZCEC08 phage identified one tRNA gene and 84 predicted genes. Comparative genomics and phylogenetic analysis suggest that the vB_Eco_ZCEC08 phage belongs to the same genus as the Salmonella phage vB_SenS_ST1 but represents a new species. Phage vB_Eco_ZCEC08 showed minimal cytotoxicity against human urinary bladder cancer and skin fibroblast cell lines.
CONCLUSION: vB_Eco_ZCEC08 phage demonstrates strong selective lytic activity against UPEC in the absence of any lysogenic behavior. These properties coupled with inherent physiochemical stability and low cytotoxicity support the development of vB_Eco_ZCEC08 as an alternative treatment for multidrug-resistant UPEC.

Keywords:  Antibiotic resistance; Artificial human urine; Molecular characterization; Phage therapy; Urinary tract infections (UTIs); Uropathogenic E. coli (UPEC)

DOI:  https://doi.org/10.1186/s12866-025-03903-x
Infect Drug Resist. 2025 ;18 1807-1818

Isolation and Characterization of a Novel Lytic Phage N22 and Its Effect on Drug-Resistant Klebsiella Pneumoniae.

Dongyu Liu, Kunhao Qin, Chengying Hong, Wei Huang, Wei Li, Puqiao Lian, Mengyao Li, Huaisheng Chen, Xueyan Liu.

   Background: Klebsiella pneumoniae (KP) infections present a significant clinical challenge and are frequently associated with elevated drug resistance. The use of phage therapy has resurged in response to escalating antibiotic resistance. This study aimed to address the multidrug resistance crisis in intensive care units by exploring the use of ceftazidime/avibactam (CAZ/AVI), a widely used clinical antimicrobial agent, in conjunction with phage therapy.
Materials and Methods: We screened a clinical strain of KP from ICU and successfully isolated phage N22 from hospital wastewater. We conducted an in-depth analysis of the physiological and biochemical properties of phage N22 and determined its optimal multiplicity of infection with the clinical KP strain. The inhibitory effects of phage N22 in combination with CAZ/AVI on biofilm formation were investigated. Comparative efficacies of these combinations were evaluated using a Galleria mellonella (G. mellonella) model.
Results: Phage N22 inhibited KP biofilm formation. The impact of varying phage N22 concentrations when used alongside CAZ/AVI was examined, and the combination of phage N22 and CAZ/AVI was more effective against KP than CAZ/AVI alone.
Conclusion: This study provides a preliminary investigation into the effects of combining CAZ/AVI with phage therapy, highlighting its potential significance in developing novel therapeutic strategies for bacterial infections resistant to CAZ/AVI. The findings underscore the importance of advancing highly effective phage agents as alternative treatment modalities for patients with infections refractory to conventional antibiotics.

Keywords:  Klebsiella pneumoniae; ceftazidime/avibactam; drug-resistant; phage therapy

DOI:  https://doi.org/10.2147/IDR.S515363
J Cyst Fibros. 2025 Apr 12. pii: S1569-1993(25)00765-9. [Epub ahead of print]

Trial design of bacteriophage therapy for nontuberculous mycobacteria pulmonary disease in cystic fibrosis: The POSTSTAMP study.

Investigators of the Cystic Fibrosis NTM Consortium

  Bacteriophages (phages) are viruses that selectively infect bacteria and have been utilized to treat Mycobacterium abscessus (Mab) with varying success. The POSTSTAMP study is an ongoing, multi-site phage therapy protocol for treatment-refractory pulmonary Mab disease in people with cystic fibrosis (pwCF). Participants (n = 10) are prospectively assessed while utilizing FDA investigational new drug (IND) approval for compassionate use. Participants are >6 years old, able to produce sputum, have been treated with guideline-based antibiotic therapy (GBT) for >12 months without culture conversion, and are currently receiving GBT with at least 3 and ≥ 80 % positive Mab cultures in the prior year. At enrollment, an isolate is assessed for the availability of lytic phage(s). Open-label phage therapy consists of 1 or 2 phages administered intravenously twice daily for 52 weeks. Participants without a phage match will be followed on GBT as a comparison group. Follow-up visits will occur monthly, with one follow-up visit at completion and intermittent visits for a year after phage therapy. Efficacy will be assessed by culture, standard clinical measures and a patient-reported quality-of-life instrument. Frequency of Mab detection 12 months prior to treatment will be compared with the 12-month period beginning 6 months after treatment initiation. Individual-level tests of difference in percent positive cultures within subjects will be used to identify "responders". Collectively and including all persons, a mixed-effect model will be used to test for a difference in frequency of Mab detection following treatment or without treatment. The trial will also test for markers of treatment failure and pathogen adaptation in participants who did not achieve microbiological response, and will monitor for safety and tolerance.

Keywords:  Biomarkers; Cystic fibrosis; M. abscessus; Nontuberculous mycobacterial (NTM); Phage therapy

DOI:  https://doi.org/10.1016/j.jcf.2025.03.669
Sci Rep. 2025 Apr 14. 15(1): 12832

Rapid formulation of a genetically diverse phage cocktail targeting uropathogenic Escherichia coli infections using the UTI89 model.

Pattida Kongsomboonchoke, Panupon Mongkolkarvin, Patiphan Khunti, Jarukit Vijitphichiankul, Poochit Nonejuie, Parameth Thiennimitr, Vorrapon Chaikeeratisak.

  Urinary tract infections are commonly caused by uropathogenic Escherichia coli (UPEC). Due to the emergence of multidrug-resistant UPEC, rendering antibiotic treatment ineffective, phage combination-based therapy has been proposed as a potential alternative. Here, we present a formulation of a genetically diverse phage-derived cocktail that is rapidly customized for UPEC using E. coli UTI89 as a model strain. Through our rapid selection and combination of four phages against UPEC strain UTI89 (SR01, SR02, SR04, and Zappy) from our library, the combination of two lytic phages, SR02 and SR04, exhibits the strongest suppression of bacterial growth for at least 16 h, with no emergence of phage resistance observed in vitro. Phage SR02 undergoes subcellular activity for 25 min, producing approximately 106 progeny particles per cell, while SR04 completes its replication cycle in 20 min, generating around 564 progeny particles per cell. These two novel phages are genetically diverse, and their cocktail exhibited potent suppression of bacterial growth, independent of multiplicities of infection (MOIs), significantly reducing the viable bacterial counts after treatment in vitro. The phage cocktail has low immunogenicity and does not induce any proinflammatory gene responses in human bladder uroepithelial cells. Moreover, the cocktail effectively eradicates the invading UPEC strain UTI89 in the uroepithelial cells at a comparable level to that of phage SR04 alone, likely releasing some immunostimulatory agents that, in turn, trigger upregulation of MIP-3 and IL-8 genes. Altogether, this study offers an alternative pipeline for rapidly formulating genetically diverse phage-derived cocktails, which is specifically customized for targeted bacteria.

Keywords:  Multidrug-resistant (MDR) bacteria; Phage cocktail, drug resistance, disease-free and overall survival ; Phage therapy; Urinary tract infection (UTI); Uropathogenic Escherichia coli (UPEC)

DOI:  https://doi.org/10.1038/s41598-025-96561-y
Crit Rev Microbiol. 2025 Apr 12. 1-15

The role of bacteriophage in inflammatory bowel disease and its therapeutic potential.

Yuyang Xiao, Xinyu Yue, Xupeng Zhang, Yifei Yang, Yibo Zhang, Lang Sun.

  Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.

Keywords:  Crohn’s disease; Inflammatory bowel disease; bacteriophage; phage therapy; ulcerative colitis

DOI:  https://doi.org/10.1080/1040841X.2025.2492154
Arch Virol. 2025 Apr 16. 170(5): 106

Characterization and genome analysis of the novel virulent Burkholderia phage Bm1, which is active against pan-drug-resistant Burkholderia multivorans.

Evgenii Rubalskii, Ludwig Sedlacek, Jan Hegermann, Leonard Knegendorf, Christina Salmoukas, Carsten Mueller, Nicolaus Schwerk, Dirk Schlüter, Arjang Ruhparwar, Christian Kuehn, Stefan Ruemke.

The escalating challenges of antibiotic resistance in bacterial pathogens have necessitated the exploration of alternative therapeutic strategies. Among these, bacteriophage therapy has regained attention as a promising approach to combat multidrug-resistant bacteria. Bacteriophages are viruses that infect and lyse specific bacterial strains, making them attractive candidates for targeted antimicrobial treatment. Burkholderia multivorans, a Gram-negative bacterium, is known to cause opportunistic infections, particularly in individuals with a compromised immune system or with cystic fibrosis. The prevalence of antibiotic-resistant Burkholderia strains has raised concerns about treatment options. In this study, we characterized the Burkholderia phage Bm1, a virulent bacteriophage isolated from an environmental source. Electron microscopy revealed that Bm1 phage particles have myovirus morphology, with an icosahedral head of 72 nm in diameter and a contractile tail of 100 nm in length and 18 nm in width. The genome of phage Bm1 consists of a double-stranded DNA of 67,539 bp with a terminal repeat region at each end. Comparative analysis indicated that the closest relative of phage Bm1 is Burkholderia phage BCSR129, with a calculated VIRIDIC identity of 57.7%. The apparent absence of an integrase gene suggests that the Burkholderia phage Bm1 has a strictly lytic life cycle.

DOI: https://doi.org/10.1007/s00705-025-06282-w
Int J Biol Macromol. 2025 Apr 12. pii: S0141-8130(25)03645-1. [Epub ahead of print] 143093

Diversity, structure-function relationships and evolution of cell wall-binding domains of staphylococcal phage endolysins.

Roberto Vázquez, Diana Gutiérrez, Bjorn Criel, Zoë Dezutter, Yves Briers.

  In response to the antibiotic resistance crisis, enzyme-based antibiotics like bacteriophage endolysins offer a promising alternative. In their natural context, endolysins lyse bacterial hosts by degrading peptidoglycan at the end of the replication cycle. They have evolved complex modular architectures, particularly in Gram-positive bacteria, featuring variable enzymatically active domains (EADs) and cell wall-binding domains (CBDs). These domains can be combinatorially shuffled to enhance antibacterial properties. CBDs are commonly seen as an important driver for the specificity of wild-type and engineered endolysins, as seen in Listeria and pneumococcal endolysins. This study explores the structural diversity and functional behavior of CBDs in endolysins from staphylococcal phages. Analysis of 182 CBDs reveals greater diversity than expected, classified into three families within the SH3b fold: SH3b_P1 (including the well-known SH3_5 family), and the new SH3b_P2 and SH3b_T families. Experimental specificity profiles of 24 CBDs using eGFP-CBD fusions against various staphylococcal species and strains challenge the notion of high host specificity within the staphylococcal context. Instead, CBDs exhibit a broader and more variable specificity and co-evolve with their accompanying EADs for functional synergy. This work provides insights for rational endolysin engineering and highlights the importance of understanding structure-function relationships to enhance their therapeutic potential.

Keywords:  Bacteriophage; Endolysin; Staphylococcus

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143093
J Food Prot. 2025 Apr 11. pii: S0362-028X(25)00060-2. [Epub ahead of print] 100508

A Review of Non-Thermal Interventions in Food Processing Technologies.

Shecoya White, Armitra Jackson-Davis, Kenisha Gordon, Kala Morris, Aaron Dudley, Angelica Abdallah-Ruiz, Katie Allgaier, Kyle Sharpe, Ajay Kumar Yenduri, Kaylyn Green, Fernanda Santos.

  Foodborne pathogens and spoilage microorganisms continue to be a concern throughout the food industry. As a result, these problematic microorganisms are the cause of foodborne outbreaks, foodborne illness, and premature spoilage related issues. To address these, thermal technologies have been applied and have a documented history of controlling these microorganisms. Although beneficial, some of these technologies may result in adverse quality effects that can interfere with consumer acceptability. Processors of fresh produce also need technologies to mitigate pathogens with the ability to retain raw quality. In addition, thermal technologies can also result in the reduction or depletion of key nutrients. Consumers of today are health conscious and are concerned with key nutrients in food products necessary for their overall health; this reduction and depletion of nutrients could be considered unacceptable in the eyes of consumers. As a result of this, the food industry works to increase the use of non-thermal technologies to control pathogens and spoilage microorganisms in varying sections of the industry. This review paper will focus on the control of foodborne pathogens and spoilage organisms along with effects on quality in various food products by use of pulsed electric field, pulsed light, ultraviolet light, ozonation, cold atmospheric plasma, ultrasound, and ionizing radiation.

Keywords:  Non-thermal technology; food processing; food quality; food safety; pathogens; spoilage

DOI:  https://doi.org/10.1016/j.jfp.2025.100508
J Basic Microbiol. 2025 Apr 16. e70036

A Review on Rare and Symbiotic Actinobacteria: Emerging Biotechnological Tools Against Antimicrobial Resistance.

Ariel Mesquita, Davi Cerqueira, Matheus Rocha, Dino Silva, Claudia Martins, Bartolomeu Souza.

  Antimicrobial resistance (AMR) poses a global threat to public health, with projections estimating 10 million deaths annually by 2050 if current trends persist. Actinobacteria, renowned for their biosynthetic capacity, are a key source of bioactive compounds, producing over 75% of known antibiotics. The adaptability of these microorganisms allows them to thrive in diverse habitats, including extreme ones, through the production of secondary metabolites that are of paramount importance for industry. Furthermore, actinobacteria are capable of living in symbiosis with several organisms, producing metabolites to protect and promote the growth of the host in exchange for nutrients and shelter. Some of these metabolites, such as antibiotics, play a key role in combating host pathogens and can be biotechnologically exploited to combat human resistant pathogens. This review presents the origins of AMR, the unique biology of actinobacteria, as well as their diverse biosynthetic pathways and their role in mitigating the AMR crisis. It also highlights the need for innovative biotechnological strategies for the isolation of rare and understudied actinobacteria, as symbiotic actinobacteria, to avoid rediscovery of molecules while finding new potential natural products and scaffolds for synthetic drugs. By providing a better understanding of their ecological, genomic, and metabolic diversity, this review provides valuable insights into the exploration of rare and symbiotic actinobacteria for developing antimicrobial solutions.

Keywords:  Actinomycetes; ESKAPE pathogens; Streptomyces; antibiotics; bioprospection

DOI:  https://doi.org/10.1002/jobm.70036
J Clin Med. 2025 Mar 30. pii: 2376. [Epub ahead of print]14(7):

Off-Label Treatment in Inflammatory Skin Diseases-European Point of View.

Julia Sternicka, Roman J Nowicki, Leszek Bieniaszewski, Dorota Purzycka-Bohdan.

  Off-label treatment is the use of a drug approved for marketing, outside the registration in terms of indication, age group, dose or route of administration. Despite the constant appearance of new preparations on the market, treatment outside the SmPCs guidelines is a current clinical problem. It is believed that it is based on the needs of patients unmet by classical therapy methods. This work focuses on off-label treatment in inflammatory dermatoses such as atopic dermatitis, psoriasis, acne vulgaris and rosacea. Publications on this subject, available on PubMed, Google Scholar and the Cochrane Library, were analyzed in the form of a review, taking into account the mechanisms of action, efficacy and safety of preparations. Based on the literature analysis, it can be concluded that the use of drugs outside the SmPC indications is a common situation in dermatology. However, it is difficult to determine its exact frequency-there is a lack of data on the prevalence of off-label appliances in inflammatory dermatoses from a European perspective. Publications demonstrate varying effectiveness and safety of this form of therapy, depending on the specific preparation. Off-label treatment in dermatology remains an important and current clinical issue that should be explored in further research.

Keywords:  acne vulgaris; atopic dermatitis; off-label; pharmacotherapy; psoriasis; rosacea

DOI:  https://doi.org/10.3390/jcm14072376
Nutrients. 2025 Mar 31. pii: 1222. [Epub ahead of print]17(7):

The Interplay Between Nutrition and Microbiota and the Role of Probiotics and Symbiotics in Pediatric Infectious Diseases.

María Slöcker-Barrio, Jesús López-Herce Cid, María José Solana-García.

  The interplay between nutrition and infectious diseases has been a central theme in health sciences for the last decades due to its great impact on the pediatric population, especially in immunocompromised patients and critically ill children. As conventional treatment and the development of antimicrobials for most infections standard treatment is either limited or not possible, alternative treatment options should be explored. Recent research shows that early enteral nutrition and nutritional supplements (such as probiotics and symbiotics) could have a pivotal role in promoting a healthy microbiome and subsequently preventing and improving outcomes for certain pediatric infectious diseases. However, understanding the specific mechanism of action and tailoring nutritional interventions remains a significant challenge. The optimal dose range for different probiotic strains and prebiotics and the most effective combination for each treatment indication needs further investigation and is yet to be defined. Additionally, in the era of personalized medicine, goal- and patient-directed treatment are key to optimizing and improving outcomes and minimizing potential complications and side effects, especially in complex and immunocompromised patients. The main objectives of this narrative review are 1. to explore the relationship and the complex interactions between microbiota and the human immune system; 2. to describe the influence of nutrition on infectious diseases; 3. to evaluate the impact of supplementation with probiotics and symbiotics in the prevention and treatment of the most relevant infections in children; and 4. to identify knowledge gaps and potential research priorities regarding the use of these supplements in pediatric patients.

Keywords:  children; immune system; infection; microbiota; nutrition; probiotic; symbiotic

DOI:  https://doi.org/10.3390/nu17071222
Bioinformation. 2024 ;20(12): 2050-2061

Insights from Shigella bacteriophage genomes analysis.

Pratanu Kayet, Surajit Bhattacharjee, Shanta Dutta, Surajit Basak.

  Shigella species, a major cause of shigellosis, remain a substantial global health issue and the emergence of antibiotic-resistant Shigella strains has aggravated the situation. Hence, four Shigella phages were investigated to provide insights into the evolutionary trajectories and genomic properties of Shigella-infecting bacteriophages using comparative genome analysis. Analysis shows that these four phages belong to the Tequatrovirus genus and include a considerable number of proteins for 'Tail' and "DNA, RNA and Nucleotide Metabolism," indicating their aptitude for specialized host interaction and replication efficiency. The identification of 10 tRNAs further support that, these phages have high replication efficiency. Thus, this study improves our understanding of phage evolution by exposing the genetic mechanisms that drive phage adaptability and host specificity. This also highlights the significance of phage genomic research in developing viable therapies for antibiotic-resistant Shigella infections.

Keywords:  Anti-CRISPR; antimicrobial resistance (AMR); functional category; shigella phage; tRNA

DOI:  https://doi.org/10.6026/9732063002002050
Breast Cancer Res Treat. 2025 Apr 17.

Targeting breast cancer: the promise of phage-based nanomedicines.

Sarah Gholami, Hossein Saffarfar, Mohammad Reza Mehraban, Nastaran Safavi Ardabili, Anis Elhami, Sara Ebrahimi, Payam Ali-Khiavi, Reza Kheradmand, Seyedeh Farinaz Fattahpour, Ahmad Mobed.

   BACKGROUND: Breast cancer is a leading cause of cancer-related mortality among women worldwide, characterized by its aggressive nature, propensity for metastasis, and resistance to standard treatment modalities. Traditional therapies, including surgery, chemotherapy, and radiation, often encounter significant limitations such as systemic toxicity and lack of specificity.
OBJECTIVE: This review aims to evaluate the recent advancements in phage-based nanomedicines as a novel approach for targeted breast cancer therapy, focusing on their mechanisms of action, therapeutic benefits, and the challenges faced in clinical implementation.
METHODS: A comprehensive literature review was conducted, analyzing studies that investigate the application of bacteriophages in cancer therapy, particularly in breast cancer. The review highlights the integration of nanotechnology with phage therapy, examining the potential for enhanced targeting and reduced side effects.
RESULTS: Phage-based nanomedicines have shown promise in selectively targeting breast cancer cells while sparing healthy tissues, thereby improving therapeutic efficacy and safety profiles. The unique properties of bacteriophages, including their ability to be engineered for specific targeting and their natural ability to induce immune responses, present significant advantages over conventional treatments.
CONCLUSION: The integration of phage therapy with nanotechnology represents a promising frontier in the fight against breast cancer. This review underscores the need for continued research to address existing challenges and to explore the full potential of phage-based nanomedicines in improving patient outcomes in breast cancer treatment.

Keywords:  Breast cancer; Nanomedicine; Nanotechnology; Phage therapy

DOI:  https://doi.org/10.1007/s10549-025-07696-5
BMC Genomics. 2025 Apr 18. 26(1): 386

Isolation and genomic characterization of Psychrobacillus isolate L3 and bacteriophage Spoks: a new phage-host pair from Antarctic soil.

Nikita Zrelovs, Karina Svanberga, Juris Jansons, Kristaps Lamsters, Janis Karuss, Maris Krievans, Davids Fridmanis, Andris Dislers, Andris Kazaks.

   BACKGROUND: Most habitats on Earth house unfathomable microbial diversity, yet much of it remains uncultured. The same applies to temperate phages, most of which documented to date are predicted purely in silico from the prophage-like genomic regions of the bacteria, lacking any experimental evidence of their functional integrity (e.g., the ability to undergo lytic replication). Hard-to-access parts of our planet with unique environments serve as especially promising places to collect samples for the isolation of novel microbes highly divergent from those isolated thus far. Antarctica, a continent mostly covered by a thick ice sheet, is one such area of our planet rife with novel microbiological entities. In this study, we aimed to isolate and characterize a novel culturable phage-host pair from Antarctic soils.
RESULTS: Psychrobacillus phage Spoks was retrieved alongside its host bacterial strain designated as "L3" from an ice-free soil sample collected at Waddington Bay, Graham Coast, Antarctica. Whole-genome sequencing of both the phage and the host revealed that they are divergent from, respectively, viruses and bacteria cultured and characterized thus far, and the intergenomic differences suggest that both might represent novel taxa. The genome of siphophage Spoks is a 36,472 bp long linear double-stranded DNA molecule with 11 base long 3' cohesive overhangs. Spoks can integrate into the chromosome of its isolation host strain in a site-specific fashion. Integration takes place in the genomic region of the host chromosome between the ORFs predicted to encode a DNA topoisomerase III and a BlaI/MecI/CopY family transcriptional regulator via recombination between attP and attB, which share a 19 bp "core" overlap sequence. L3 lysogens containing Spoks are not stable, with regular spontaneous induction occurring. Although the attachment site overlap sequence was found in the publicly available genomic sequences of several other Psychrobacillus spp. strains isolated from different habitats, none were found to contain a Spoks-like prophage.
CONCLUSIONS: The isolation and characterization of Psychrobacillus temperate phage Spoks and its host strain L3 from Antarctica highlight the potential for discovering novel biological entities divergent from their closest cultured relatives with relative ease, given access to such difficult-to-access undersampled environments, and are expected to encourage similar studies.

Keywords:   Caudoviricetes ; Psychrobacillus ; Antarctica; Genomics; Integration; Lysogeny; Prophage; Sequencing; Temperate phage

DOI:  https://doi.org/10.1186/s12864-025-11425-z
Appl Environ Microbiol. 2025 Apr 16. e0178824

The human phageome: niche-specific distribution of bacteriophages and their clinical implications.

Izabela Rybicka, Zuzanna Kaźmierczak.

  Bacteriophages (phages) play a crucial role in shaping the composition and diversity of the human microbiome across various body niches. Recent advancements in high-throughput sequencing technologies have enabled comprehensive analysis of the human phageome in different body sites. This review comprehensively analyzes phage populations across major human body niches, examining their distribution and dynamics through recent metagenomic discoveries. We explore how phage-bacteria interactions within different body sites contribute to homeostasis and disease development. Emerging evidence demonstrates that phageome perturbations can serve as early indicators of various disorders, particularly in the gut microbiome. Understanding these complex microbial interactions offers promising opportunities for developing novel diagnostic markers and therapeutic approaches. However, the causal relationship between phages, bacteria, and disease development remains unclear. Further research is needed to elucidate the role of phages in human health and disease and to explore their potential as diagnostic or therapeutic tools. Understanding the intricate interactions between phages, bacteria, and the human host is crucial for unraveling the complexities of the human microbiome and its impact on health and disease.

Keywords:  bacteriophages; high-throughput sequencing; human microbiome; metagenomics; phageome

DOI:  https://doi.org/10.1128/aem.01788-24
FEMS Microbiol Ecol. 2025 Apr 18. pii: fiaf043. [Epub ahead of print]

Weberviruses are gut-associated phages that infect Klebsiella spp.

Samuel J T Dawson, Preetha Shibu, Sara Garnett, Fiona Newberry, Thomas C Brook, Tobi Tijani, Magdalena Kujawska, Lindsay J Hall, Anne L McCartney, David Negus, Lesley Hoyles.

  Weberviruses are bacteriophages (phages) that can infect and lyse clinically relevant, multidrug-resistant (MDR) strains of Klebsiella. They are an attractive therapeutic option to tackle Klebsiella infections due to their high burst sizes, long shelf life and associated depolymerases. In this study we isolated and characterized seven new lytic phages and compared their genomes with those of their closest relatives. Gene-sharing network, ViPTree proteome and terL gene-sequence-based analyses incorporating all publicly available webervirus genomes [n=258 from isolates, n=65 from metagenome-assembled genome (MAG) datasets] confirmed the seven phages as members of the genus Webervirus and identified a novel genus (Defiantjazzvirus) within the family Drexlerviridae. Using our curated database of 265 isolated phage genomes and 65 MAGs (n=330 total), we found that weberviruses are distributed globally and primarily associated with samples originating from the gut: sewage (154/330, 47%), wastewater (83/330, 25%) and human faeces (66/330, 20%). We identified three distinct clusters of potential depolymerases encoded within the 330 genomes. Due to their global distribution, frequency of isolation and lytic activity against the MDR clinical Klebsiella strains used in this study, we conclude that weberviruses and their depolymerases show promise for development as therapeutic agents against Klebsiella spp.

Keywords:   Klebsiella pneumoniae ; comparative genomics; environment; metagenome-assembled genomes; microbiota

DOI:  https://doi.org/10.1093/femsec/fiaf043
Microb Pathog. 2025 Apr 16. pii: S0882-4010(25)00333-X. [Epub ahead of print] 107608

A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites.

Md Mizanur Rahaman, Phurpa Wangchuk, Subir Sarker.

  Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD patients and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Keywords:  Bacteriophage; IBD; Microbiome; Plant metabolites; Virome

DOI:  https://doi.org/10.1016/j.micpath.2025.107608
Microb Pathog. 2025 Apr 16. pii: S0882-4010(25)00330-4. [Epub ahead of print] 107605

Acinetobacter baumannii: A Comprehensive Review of Global Epidemiology, Clinical Implications, Host Interactions, Mechanisms of Antimicrobial Resistance and Mitigation Strategies.

Rhythm Sharma, Dinesh Lakhanpal.

  Since the discovery of Acinetobacter baumannii, it has emerged as a significant global health threat due to its increasing prevalence in healthcare settings and remarkable ability to develop resistance to various antibiotics. This detailed review addresses global epidemiology, emphasizing the worldwide distribution of carbapenem-resistant A. baumannii (CRAb), which is particularly prevalent in high-density healthcare settings and regions with intensive antibiotic usage, such as India. Clinically, A. baumannii infection poses serious health challenges, with mortality rates ranging from 30% to 75% for multidrug-resistant (MDR) strains. The review highlights the clinical impact and disease spectrum of A. baumannii, associated with pneumonia, wound infections, bloodstream infections, and, urinary tract infections with a strong association to invasive medical procedures and devices. Additionally, it discusses human-pathogen interactions by exploring various mechanisms, persistence in hospital environments, and survival under harsh conditions. The review further elaborates on different resistance mechanisms, focusing broadly on antibiotic degradation, altered drug targets, reduced drug permeability, and efflux systems, which facilitate the survival and persistence of A. baumannii. Finally, it evaluates strategies to combat AMR, emphasizing infection control measures, antimicrobial stewardship, and the urgent need for innovative therapeutic approaches such as phage therapy and new antibiotic development. The review calls for concerted, collaborative efforts among researchers, healthcare professionals, and public health authorities to mitigate the global threat posed by MDR A. baumannii strains.

Keywords:  Antimicrobial resistance; Extensively-drug-resistant; Intensive care units; Multidrug-resistant; Nosocomial infections; Pan-drug-resistant; Pneumonia; Urinary-tract infections; β-lactam antibiotics

DOI:  https://doi.org/10.1016/j.micpath.2025.107605