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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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 languageEnglish (US)
Pages (from-to)855-861
Number of pages7
JournalNature Chemical Biology
Volume8
Issue number10
DOIs
StatePublished - Sep 3 2012

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Wang, X., Lord, D. M., Cheng, H. Y., Osbourne, D. O., Hong, S. H., Sanchez-Torres, V., Quiroga, C., Zheng, K., Herrmann, T., Peti, W., Benedik, M. J., Page, R., & Wood, T. K. (2012). A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nature Chemical Biology, 8(10), 855-861. https://doi.org/10.1038/nchembio.1062