Conservation of Putative Liquid-Liquid Phase Separating Proteins in Multiple Drug-Resistant Mycobacterium tuberculosis: Role in Host-Pathogen Interactions?

IF 4 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-04-04 DOI:10.1021/acsinfecdis.4c00722

Jasdeep Singh, Prashant Pradhan, Arti Kataria, Sanjeev Sinha, Nasreen Z Ehtesham, Peter N Monk, Seyed E Hasnain

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Abstract

We observed a high proportion of proteins in pathogenic Mycobacterium species that can potentially undergo liquid-liquid phase separation (LLPS) mediated biomolecular condensate formation, compared to nonpathogenic species. These proteins mainly include the PE-PPE and PE-PGRS families of proteins that have nucleic acid and protein-protein binding functions, typical of LLPS proteins. We also mapped identified LLPS proteins in M. tuberculosis (M.tb) drug-resistant databases PubMLST and TBProfiler, based upon the WHO 2023 catalogue of resistance-associated mutations. High sequence conservation of LLPS-associated proteins in various multiple drug-resistant M.tb isolates points to their potentially important role in virulence and host-pathogen interactions during pathogenic evolution. This analysis provides a perspective on the role of protein phase separation in the evaluation of M.tb pathogenesis and offers avenues for future research aimed at developing innovative strategies to combat M.tb infection.

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多重耐药结核分枝杆菌中假定的液-液相分离蛋白的保存：在宿主-病原体相互作用中的作用？

我们观察到，与非致病性分枝杆菌相比，致病性分枝杆菌中有很高比例的蛋白质可能经历液-液相分离（LLPS）介导的生物分子凝聚形成。这些蛋白主要包括PE-PPE和PE-PGRS蛋白家族，具有核酸和蛋白蛋白结合功能，典型的LLPS蛋白。我们还根据WHO 2023耐药相关突变目录，在结核分枝杆菌耐药数据库PubMLST和TBProfiler中绘制了鉴定的LLPS蛋白。在多种多重耐药结核分枝杆菌分离株中llps相关蛋白的高序列保守性表明它们在致病进化过程中在毒力和宿主-病原体相互作用中可能发挥重要作用。这一分析为蛋白质相分离在结核分枝杆菌发病机制评价中的作用提供了一个视角，并为未来的研究提供了旨在制定抗结核分枝杆菌感染的创新策略的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.