Rv0684/fusA1, an Essential Gene, Is the Target of Fusidic Acid and Its Derivatives in Mycobacterium tuberculosis

被引：10

作者：

Singh, Vinayak ^{[2
,3
,4
]}

Dziwornu, Godwin Akpeko ^{[1
,2
]}

Mabhula, Amanda ^{[1
,2
,3
]}

Chibale, Kelly ^{[2
,3
,4
]}

机构：

[1] Univ Cape Town, South African Med Res Council, Drug Discovery & Dev Res Unit, ZA-7701 Rondebosch, South Africa

[2] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa

[3] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa

[4] Univ Cape Town, Drug Discovery & Dev Ctr H3D, South African Med Res Council, Drug Discovery & Dev Res Unit, ZA-7701 Rondebosch, South Africa

来源：

ACS INFECTIOUS DISEASES | 2021年 / 7卷 / 08期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

Tuberculosis; Mycobacterium tuberculosis; antituberculars; elongation factor G; Fusidic acid; MOLECULAR DOCKING; AMIDE DERIVATIVES; BINDING-SITE; ELONGATION; AGENTS;

D O I：

10.1021/acsinfecdis.1c00195

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern given the increase in multiple forms of drug-resistant TB. This underscores the importance of a continuous pipeline of new anti-TB agents. Drug repurposing has shown promise in expanding the therapeutic options for TB chemotherapy. Fusidic acid (FA), a natural product-derived antibiotic, is one such candidate for repurposing. The present study aimed to understand the mechanism of action of FA and its selected analogs in M. tuberculosis. By using chemical biology and genetics, we identified elongation factor G as the target of FA in M. tuberculosis. We showed essentiality of its encoding gene fusA1 in M. tuberculosis by demonstrating that the transcriptional silencing of fusA1 is bactericidal in vitro and in macrophages. Thus, this work validated a novel drug target FusA1 in M. tuberculosis.

引用

页码：2437 / 2444

页数：8

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