A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA

被引：185

作者：

Cheverton, Angela M. ^{[1
]}

Gollan, Bridget ^{[1
]}

Przydacz, Michal ^{[2
]}

Wong, Chi T. ^{[2
]}

Mylona, Anastasia ^{[1
]}

Hare, Stephen A. ^{[2
]}

Helaine, Sophie ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Sect Microbiol, Med Res Council, Ctr Mol Bacteriol & Infect, London SW7 2AZ, England

[2] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England

来源：

MOLECULAR CELL | 2016年 / 63卷 / 01期

基金：

英国医学研究理事会;

关键词：

AMINOACYL-TRANSFER-RNA; BACTERIAL PERSISTENCE; STOCHASTIC INDUCTION; INHIBITS TRANSLATION; ANTITOXIN SYSTEMS; ESCHERICHIA-COLI; HYDROLASE; CELLS; COOPERATIVITY; ENDONUCLEASES;

D O I：

10.1016/j.molcel.2016.05.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The recalcitrance of many bacterial infections to antibiotic treatment is thought to be due to the presence of persisters that are non-growing, antibiotic-insensitive cells. Eventually, persisters resume growth, accounting for relapses of infection. Salmonella is an important pathogen that causes disease through its ability to survive inside macrophages. After macrophage phagocytosis, a significant proportion of the Salmonella population forms non-growing persisters through the action of toxin-antitoxin modules. Here we reveal that one such toxin, TacT, is an acetyltransferase that blocks the primary amine group of amino acids on charged tRNA molecules, thereby inhibiting translation and promoting persister formation. Furthermore, we report the crystal structure of TacT and note unique structural features, including two positively charged surface patches that are essential for toxicity. Finally, we identify a detoxifying mechanism in Salmonella wherein peptidyl-tRNA hydrolase counteracts TacT-dependent growth arrest, explaining how bacterial persisters can resume growth.

引用

页码：86 / 96

页数：11

共 37 条

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