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

Xiaoxue Wang; Dana M. Lord; Hsin Yao Cheng; Devon O. Osbourne; Seok Hoon Hong; Viviana Sanchez-Torres; Cecilia Quiroga; Kevin Zheng; Torsten Herrmann; Wolfgang Peti; Michael J. Benedik; Rebecca Page; Thomas K. Wood

doi:10.1038/nchembio.1062

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

Xiaoxue Wang, Dana M. Lord, Hsin Yao Cheng, Devon O. Osbourne, Seok Hoon Hong, Viviana Sanchez-Torres, Cecilia Quiroga, Kevin Zheng, Torsten Herrmann, Wolfgang Peti, Michael J. Benedik, Rebecca Page, Thomas K. Wood

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248 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	855-861
Number of pages	7
Journal	Nature Chemical Biology
Volume	8
Issue number	10
DOIs	https://doi.org/10.1038/nchembio.1062
State	Published - 2012

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1038/nchembio.1062

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@article{06a4754ec7864572a2fba8f32349eae9,

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

abstract = "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.",

author = "Xiaoxue Wang and Lord, {Dana M.} and Cheng, {Hsin Yao} and Osbourne, {Devon O.} and Hong, {Seok Hoon} and Viviana Sanchez-Torres and Cecilia Quiroga and Kevin Zheng and Torsten Herrmann and Wolfgang Peti and Benedik, {Michael J.} and Rebecca Page and Wood, {Thomas K.}",

note = "Funding Information: This work was supported by the US National Institutes of Health (R01 GM089999 to T.K.W.) and the US National Science Foundation (CAREER award MCB 0952550 to R.P.). X.W. is partially supported by the 1000-Youth Elite Program from China. We are grateful for the Keio and ASKA strains provided by the Genome Analysis Project in Japan and for the initial growth studies conducted by X. Yan and T. Benefield. We also thank S. Vitha for assistance with microscope imaging and Y. Hu for assistance with western blotting. T.K.W. is the Biotechnology Endowed Professor at the Pennsylvania State University.",

year = "2012",

doi = "10.1038/nchembio.1062",

language = "English (US)",

volume = "8",

pages = "855--861",

journal = "Nature Chemical Biology",

issn = "1552-4450",

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T1 - A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS

AU - Wang, Xiaoxue

AU - Lord, Dana M.

AU - Cheng, Hsin Yao

AU - Osbourne, Devon O.

AU - Hong, Seok Hoon

AU - Sanchez-Torres, Viviana

AU - Quiroga, Cecilia

AU - Zheng, Kevin

AU - Herrmann, Torsten

AU - Peti, Wolfgang

AU - Benedik, Michael J.

AU - Page, Rebecca

AU - Wood, Thomas K.

N1 - Funding Information: This work was supported by the US National Institutes of Health (R01 GM089999 to T.K.W.) and the US National Science Foundation (CAREER award MCB 0952550 to R.P.). X.W. is partially supported by the 1000-Youth Elite Program from China. We are grateful for the Keio and ASKA strains provided by the Genome Analysis Project in Japan and for the initial growth studies conducted by X. Yan and T. Benefield. We also thank S. Vitha for assistance with microscope imaging and Y. Hu for assistance with western blotting. T.K.W. is the Biotechnology Endowed Professor at the Pennsylvania State University.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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JO - Nature Chemical Biology

JF - Nature Chemical Biology

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ER -

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

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