Metabolic Tagging Reveals Surface-Associated Lipoproteins in Mycobacteria.

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-09-12 DOI:10.1021/acsinfecdis.5c00365

Lia A Parkin, Kindra L Becker, Julian P Maceren, Aseem Palande, Neetika Jaisinghani, Mary L Previti, Jessica C Seeliger

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Abstract

Mycobacteria such as the causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), encode over 100 bioinformatically predicted lipoproteins. Despite the importance of these post-translationally modified proteins for mycobacterial survival, many remain experimentally unconfirmed. Here we characterized in Mtb and M. smegmatis (Msm) the metabolic incorporation of several modified fatty acids as a facile method of adding chemical groups that enable downstream applications such as detection and enrichment of lipid-modified proteins. We further showed for azido palmitic acid in Msm that incorporation is an active process dependent on the lipoprotein biosynthesis pathway and that a subset of these lipid-modified proteins are associated with the mycobacterial cell surface. Because mycobacteria do not encode known lipoprotein transporters, these data have implications for uncovering the roles of lipoproteins and the possible transport processes involved. Our findings and the tools we validated will enable the further study of pathways related to lipoprotein function in mycobacteria and other bacteria in which lipoproteins remain poorly understood.

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代谢标记揭示分枝杆菌表面相关脂蛋白。

分枝杆菌，如结核的病原体，结核分枝杆菌（Mtb），编码超过100种生物信息学预测的脂蛋白。尽管这些翻译后修饰蛋白对分枝杆菌的存活很重要，但许多仍未得到实验证实。在这里，我们在结核分枝杆菌和耻垢分枝杆菌（Msm）中描述了几种修饰脂肪酸的代谢结合，作为添加化学基团的简便方法，使下游应用如脂质修饰蛋白的检测和富集成为可能。我们进一步表明，在Msm中，叠氮棕榈酸的掺入是一个依赖于脂蛋白生物合成途径的活跃过程，并且这些脂质修饰蛋白的一个子集与分枝杆菌细胞表面相关。由于分枝杆菌不编码已知的脂蛋白转运蛋白，这些数据对揭示脂蛋白的作用和可能涉及的转运过程具有重要意义。我们的发现和我们验证的工具将有助于进一步研究分枝杆菌和其他对脂蛋白知之甚少的细菌中与脂蛋白功能相关的途径。

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.