{"title":"Characterization of a novel virulent mycobacteriophage Kashi-SSH1 (KSSH1) depicting genus-specific broad-spectrum anti-mycobacterial activity","authors":"Tanmayee Nayak , Anuja Kakkar , Lav Kumar Jaiswal , Garima Kandwal , Anand Kumar Singh , Louise Temple , Ankush Gupta","doi":"10.1016/j.lfs.2025.123546","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><div>Tuberculosis (TB) is one of the leading infectious disease causing mortality in the world and the rise of drug resistance; multi-drug resistance (MDR) and extensive-drug resistance (XDR) has added to extra complicacy of the disease. In this scenario, phage therapy has emerged as a potential treatment option against drug-sensitive/-resistant strains.</div></div><div><h3>Materials and methods</h3><div>The mycobacteriophage Kashi-SSH1 (KSSH1) was isolated from soil sample and was genomically, phenotypically, and functionally characterized. It includes genome assembly/annotation, transmission electron microscopy, multiplicity of infection (MOI), one-step growth curve, temperature/pH stability, confocal microscopy, host range determination and host growth reduction assays.</div></div><div><h3>Key findings</h3><div>KSSH1 is a novel polyvalent virulent mycobacteriophage from the <em>Myoviridae</em> family, classified under cluster C1 with a 155,659 bp genome carrying key lysis genes—Holliday junction resolvase, Holin, Lysin A, and Lysin B, has an optimal MOI of 0.01, a 60-min latent period, and a burst size of 200 phages/bacterial cell. It remains stable up to 55 °C and within pH 7–10, exhibiting broad-spectrum activity against <em>Mycobacterium</em> species, like <em>M. fortuitum</em> (opportunistic pathogen), <em>M. tuberculosis</em> H37Ra (attenuated pathogen), and <em>M. smegmatis</em>, but not non-mycobacterial hosts. KSSH1 exhibits comparable growth inhibition of <em>M. smegmatis</em> like the antibiotics isoniazid and rifampicin as compared to the control, in liquid cultures for over 50 h without regrowth.</div></div><div><h3>Significance</h3><div>KSSH1 exhibits strong lytic activity against various <em>Mycobacterium</em> species, lacks lysogeny-associated genes like integrases/transcriptional repressors, antibiotic resistance and virulence genes and remains stable from 4 °C to 37 °C and pH 8–10 ensuring safety/stability making it an ideal candidate for therapeutic use.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123546"},"PeriodicalIF":5.1000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525001808","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Aim
Tuberculosis (TB) is one of the leading infectious disease causing mortality in the world and the rise of drug resistance; multi-drug resistance (MDR) and extensive-drug resistance (XDR) has added to extra complicacy of the disease. In this scenario, phage therapy has emerged as a potential treatment option against drug-sensitive/-resistant strains.
Materials and methods
The mycobacteriophage Kashi-SSH1 (KSSH1) was isolated from soil sample and was genomically, phenotypically, and functionally characterized. It includes genome assembly/annotation, transmission electron microscopy, multiplicity of infection (MOI), one-step growth curve, temperature/pH stability, confocal microscopy, host range determination and host growth reduction assays.
Key findings
KSSH1 is a novel polyvalent virulent mycobacteriophage from the Myoviridae family, classified under cluster C1 with a 155,659 bp genome carrying key lysis genes—Holliday junction resolvase, Holin, Lysin A, and Lysin B, has an optimal MOI of 0.01, a 60-min latent period, and a burst size of 200 phages/bacterial cell. It remains stable up to 55 °C and within pH 7–10, exhibiting broad-spectrum activity against Mycobacterium species, like M. fortuitum (opportunistic pathogen), M. tuberculosis H37Ra (attenuated pathogen), and M. smegmatis, but not non-mycobacterial hosts. KSSH1 exhibits comparable growth inhibition of M. smegmatis like the antibiotics isoniazid and rifampicin as compared to the control, in liquid cultures for over 50 h without regrowth.
Significance
KSSH1 exhibits strong lytic activity against various Mycobacterium species, lacks lysogeny-associated genes like integrases/transcriptional repressors, antibiotic resistance and virulence genes and remains stable from 4 °C to 37 °C and pH 8–10 ensuring safety/stability making it an ideal candidate for therapeutic use.
期刊介绍：
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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