A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS

被引：244

作者：

Wang, Xiaoxue ^{[2
,3
]}

Lord, Dana M. ^{[4
]}

Cheng, Hsin-Yao ^{[5
]}

Osbourne, Devon O. ^{[5
]}

Hong, Seok Hoon ^{[3
]}

Sanchez-Torres, Viviana ^{[3
]}

Quiroga, Cecilia ^{[5
]}

Zheng, Kevin ^{[1
]}

Herrmann, Torsten ^{[6
]}

Peti, Wolfgang ^{[4
]}

Benedik, Michael J. ^{[7
]}

Page, Rebecca ^{[1
]}

Wood, Thomas K. ^{[3
,5
,8
]}

机构：

[1] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA

[2] Chinese Acad Sci, S China Sea Inst Oceanol, Key Lab Marine Bioresources Sustainable Utilizat, Guangzhou, Guangdong, Peoples R China

[3] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA

[4] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA

[5] Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA

[6] Univ Lyon, Ctr Europeen Resonance Magnet Nucl Tres Champ, CNRS, Ecole Normale Super Lyon, Lyon, France

[7] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA

[8] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

来源：

NATURE CHEMICAL BIOLOGY | 2012年 / 8卷 / 10期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

GENERAL STRESS-RESPONSE; NMR STRUCTURE DETERMINATION; ESCHERICHIA-COLI; BACTERIAL PERSISTENCE; MULTIDRUG TOLERANCE; BIOFILM FORMATION; PROTEIN; EXPRESSION; CELLS; REGULATOR;

D O I：

10.1038/NCHEMBIO.1062

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：

Among bacterial toxin-antitoxin systems, to date no antitoxin has been identified that functions by cleaving toxin mRNA. Here we show that YjdO (renamed GhoT) is a membrane lytic peptide that causes ghost cell formation (lysed cells with damaged membranes) and increases persistence (persister cells are tolerant to antibiotics without undergoing genetic change). GhoT is part of a new toxin-antitoxin system with YjdK (renamed GhoS) because in vitro RNA degradation studies, quantitative real-time reverse-transcription PCR and whole-transcriptome studies revealed that GhoS masks GhoT toxicity by cleaving specifically yjdO (ghoT) mRNA. Alanine substitutions showed that Arg28 is important for GhoS activity, and RNA sequencing indicated that the GhoS cleavage site is rich in U and A. The NMR structure of GhoS indicates it is related to the CRISPR-associated-2 RNase, and GhoS is a monomer. Hence, GhoT-GhoS is to our knowledge the first type V toxin-antitoxin system where a protein antitoxin inhibits the toxin by cleaving specifically its mRNA.

引用

页码：855 / 861

页数：7

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