The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis

Q1 Immunology and Microbiology

Cell Surface Pub Date : 2024-10-15 DOI:10.1016/j.tcsw.2024.100132

Nabiela Moolla , Helen Weaver , Rebeca Bailo , Albel Singh , Vassiliy N. Bavro , Apoorva Bhatt

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Abstract

The Mycobacterium tuberculosis virulence lipid phthiocerol dimycocerosate (PDIM) is exported by a complex mechanism that involves multiple proteins including the Resistance-Nodulation-Division (RND) transporter MmpL7 and the lipoprotein LppX. Here, we probe the role of the putative heterooligomeric ATP-Binding Cassette (ABC) transporter complex composed of DrrA, DrrB and DrrC in PDIM transport by constructing a set of individual null mutants of drrA, drrB and drrC in the vaccine strain Mycobacterium bovis BCG. Loss of all three, or individual drr genes, all resulted in a complete loss of PDIM export to the outer envelope of the mycobacterial cell. Furthermore, guided by a bioinformatic analysis we interrogated specific signature residues within the DrrABC to demonstrate that it is indeed an ABC transporter, and our modelling, together with the mutagenesis identify it as a member of the Type V family of ABC exporters. We identify several unique structural elements of the transporter, including a non-canonical C-terminally inserted domain (CTD) structure within DrrA, which may account for its functional properties.

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ABC 转运体 DrrABC 在结核分枝杆菌 PDIM 的输出过程中的作用

结核分枝杆菌毒力脂质酞酰芹醇二甲芹糖酯（PDIM）的输出机制复杂，涉及多种蛋白质，包括抗性-结节-分裂（RND）转运体 MmpL7 和脂蛋白 LppX。在这里，我们通过在疫苗菌株卡介苗中构建一组 drrA、drrB 和 drrC 的单个无效突变体，探究了由 DrrA、DrrB 和 DrrC 组成的假定异源同源 ATP 结合盒（ABC）转运体复合物在 PDIM 转运中的作用。所有三个或单个 drr 基因的缺失都会导致 PDIM 完全丧失向分枝杆菌细胞外包膜的输出。此外，在生物信息学分析的指导下，我们询问了 DrrrABC 中的特定特征残基，证明它确实是 ABC 转运体，我们的建模和诱变确定它是 ABC 转运体 V 型家族的成员。我们确定了该转运体的几个独特结构元素，包括 DrrA 中的非经典 C 端插入结构域 (CTD)，这可能是其功能特性的原因。

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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