Journal Article

A Common Origin for the Bacterial Toxin-Antitoxin Systems parD and ccd, Suggested by Analyses of Toxin/Target and Toxin/Antitoxin Interactions

Mitchenall, Lesley A., López-Villarejo, Juan, Maxwell, Anthony, Díaz-Orejas, Ramón, Lemonnier, Marc, Barendregt, Arjan, Smith, Andrew B., Diago-Navarro, Elizabeth, Heck, Albert J.

2012

Overview

Bacterial toxin-antitoxin (TA) systems encode two proteins, a potent inhibitor of cell proliferation (toxin) and its specific antidote (antitoxin). Structural data has revealed striking similarities between the two model TA toxins CcdB, a DNA gyrase inhibitor encoded by the ccd system of plasmid F, and Kid, a site-specific endoribonuclease encoded by the parD system of plasmid R1. While a common structural fold seemed at odds with the two clearly different modes of action of these toxins, the possibility of functional crosstalk between the parD and ccd systems, which would further point to their common evolutionary origin, has not been documented. Here, we show that the cleavage of RNA and the inhibition of protein synthesis by the Kid toxin, two activities that are specifically counteracted by its cognate Kis antitoxin, are altered, but not inhibited, by the CcdA antitoxin. In addition, Kis was able to inhibit the stimulation of DNA gyrase-mediated cleavage of DNA by CcdB, albeit less efficiently than CcdA. We further show that physical interactions between the toxins and antitoxins of the different systems do occur and define the stoichiometry of the complexes formed. We found that CcdB did not degrade RNA nor did Kid have any reproducible effect on the tested DNA gyrase activities, suggesting that these toxins evolved to reach different, rather than common, cellular targets.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antitoxins / Bacteria / Bacterial Proteins - chemistry / Bacterial Proteins - genetics / Biological evolution / Biology / Cell proliferation / Chloramphenicol - chemistry / Cleavage / Coding / Crosstalk / Deoxyribonucleic acid / DNA / DNA Cleavage / DNA topoisomerase / DNA, Circular - chemistry / DNA-Binding Proteins - chemistry / DNA-Binding Proteins - genetics / E coli / Enzyme Stability / Escherichia coli / Escherichia coli - enzymology / Escherichia coli - genetics / Escherichia coli Proteins - chemistry / Escherichia coli Proteins - genetics / Evolution, Molecular / Health aspects / Inhibitors / Luciferases - biosynthesis / Mass spectrometry / Molecular biology / Molecular Weight / Pharmaceutical sciences / Plasmids / Protein Binding / Protein biosynthesis / Protein Biosynthesis - drug effects / Protein synthesis / Protein Synthesis Inhibitors - chemistry / Proteins / Proteomics / Ribonucleic acid / RNA / RNA Cleavage / RNA, Bacterial - chemistry / Scientific imaging / Stoichiometry / Toxins / Toxins and antitoxins