Ionophore A23187 shows anti-tuberculosis activity and synergy with tebipenem

被引：8

作者：

Huang, Wei ^{[1
,2
]}

Briffotaux, Julien ^{[1
]}

Wang, Xinwei ^{[1
]}

Liu, Lili ^{[1
]}

Hao, Pei ^{[1
]}

Cimino, Mena ^{[2
]}

Buchieri, Maria Virginia ^{[2
]}

Namouchi, Amine ^{[2
]}

Ainsa, Jose-Antonio ^{[3
,4
,5
]}

Gicquel, Brigitte ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Inst Pasteur Shanghai, Emerging Bacterial Pathogens Unit, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China

[2] Inst Pasteur, Mycobacterial Genet Unit, Paris, France

[3] Univ Zaragoza, Dept Microbiol, Zaragoza, Spain

[4] Univ Zaragoza, BIFI, Zaragoza, Spain

[5] Inst Salud Carlos III, CIBERES, Madrid, Spain

来源：

TUBERCULOSIS | 2017年 / 107卷

关键词：

MYCOBACTERIUM-TUBERCULOSIS; RESISTANCE; DRUGS; SUSCEPTIBILITY; SALINOMYCIN; CONVERSION; VIRULENCE; FAMILY; MODEL;

D O I：

10.1016/j.tube.2017.09.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The objective of this study was to find molecules with anti-mycobacterial activity from a natural compounds library, investigate their mechanisms of resistance, and assess their synergy with antibiotics. We screened a library of 2582 natural compounds with Mycobacterium aurum with the aim of identifying molecules with anti-mycobacterial activity. The hits with the lowest MICs in M. aurum were also tested for their antimicrobial activity in other mycobacterial species including M. tuberculosis complex strains. The chequerboard titration assay was chosen for determining drug interactions in vitro. Spontaneous resistant mutants were isolated and their whole genome sequences compared to wild type and resistant mutants to identify resistance mechanisms. We found that ionophores show anti-mycobacterial activity in vitro. Resistance mechanism to ionophores is mediated by the MmpL5-MmpS5 transporter over-expression. Ionophore A23187 enhanced beta-lactam activity in M. tuberculosis infected macrophage. It will help in the investigation of new drug combinations against bacterial infections including tuberculosis. (c) 2017 Elsevier Ltd. All rights reserved.

引用

页码：111 / 118

页数：8

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