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全基因组筛选以发现印度斯坦分枝杆菌中的新型毒素-抗毒素模块;分枝杆菌进化过程中基因获得的研究视角

Genome wide screening to discover novel toxin-antitoxin modules in Mycobacterium indicus pranii; perspective on gene acquisition during mycobacterial evolution.

作者信息

Bahl Aayush, Rakshit Roopshali, Pandey Saurabh, Tripathi Deeksha

机构信息

Microbial Pathogenesis and Microbiome Lab, Department of Microbiology, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India.

Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, Delhi, India.

出版信息

Biotechnol Appl Biochem. 2025 Feb;72(1):116-137. doi: 10.1002/bab.2651. Epub 2024 Aug 7.

Abstract

Mycobacterium indicus pranii (MIP), a benign saprophyte with potent immunomodulatory attributes, holds a pivotal position in mycobacterial evolution, potentially serving as the precursor to the pathogenic Mycobacterium avium complex (MAC). Despite its established immunotherapeutic efficacy against leprosy and notable outcomes in gram-negative sepsis and COVID-19 cases, the genomic and biochemical features of MIP remain largely elusive. This study explores the uncharted territory of toxin-antitoxin (TA) systems within MIP, hypothesizing their role in mycobacterial pathogenicity regulation. Genome-wide screening, employing diverse databases, unveils putative TA modules in MIP, setting the stage for a comparative analysis with known modules in Mycobacterium tuberculosis, Mycobacterium smegmatis, Escherichia coli, and Vibrio cholerae. The study further delves into the TA network of MAC and Mycobacterium intracellulare, unraveling interactive properties and family characteristics of identified TA modules in MIP. This comprehensive exploration seeks to illuminate the contribution of TA modules in regulating virulence, habitat diversification, and the evolutionary pathogenicity of mycobacteria. The insights garnered from this investigation not only enhance our understanding of MIP's potential as a vaccine candidate but also hold promise in optimizing tuberculosis drug regimens for expedited recovery.

摘要

印度斯坦分枝杆菌(MIP)是一种具有强大免疫调节特性的良性腐生菌,在分枝杆菌进化中占据关键地位,可能是致病性鸟分枝杆菌复合群(MAC)的前身。尽管MIP对麻风病具有既定的免疫治疗效果,且在革兰氏阴性败血症和新冠肺炎病例中取得了显著成果,但其基因组和生化特征在很大程度上仍不明确。本研究探索了MIP中毒素-抗毒素(TA)系统这一未知领域,推测它们在分枝杆菌致病性调控中的作用。通过使用多种数据库进行全基因组筛选,揭示了MIP中假定的TA模块,为与结核分枝杆菌、耻垢分枝杆菌、大肠杆菌和霍乱弧菌中已知模块进行比较分析奠定了基础。该研究进一步深入研究了MAC和胞内分枝杆菌的TA网络,揭示了MIP中已鉴定TA模块的相互作用特性和家族特征。这一全面探索旨在阐明TA模块在调节分枝杆菌毒力、栖息地多样化和进化致病性方面的作用。从这项研究中获得的见解不仅增强了我们对MIP作为疫苗候选物潜力的理解,也有望优化结核病药物治疗方案以加速康复。

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