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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

250 Citations (Scopus)

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
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
Publication status	Published - 2012
Externally published	Yes

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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.}",

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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.

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

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