Expression of different ParE toxins results in conserved phenotypes with distinguishable classes of toxicity

Microbiologyopen. 2019 Oct;8(10):e902. doi: 10.1002/mbo3.902. Epub 2019 Jul 16.

Abstract

Toxin-antitoxin (TA) systems are found on both chromosomes and plasmids. These systems are unique in that they can confer both fatal and protective effects on bacterial cells-a quality that could potentially be harnessed given further understanding of these TA mechanisms. The current work focuses on the ParE subfamily, which is found throughout proteobacteria and has a sequence identity on average of approximately 12% (similarity at 30%-80%). Our aim is to evaluate the equivalency of chromosomally derived ParE toxin activity depending on its bacterial species of origin. Nine ParE toxins were analyzed, originating from six different bacterial species. Based on the resulting toxicity, three categories can be established: ParE toxins that do not exert toxicity under the experimental conditions, toxins that exert toxicity within the first four hours, and those that exert toxicity only after 10-12 hr of exposure. All tested ParE toxins produce a cellular morphologic change from rods to filaments, consistent with disruption of DNA topology. Analysis of the distribution of filamented cells within a population reveals a correlation between the extent of filamentation and toxicity. No membrane septation is visible along the length of the cell filaments, whereas aberrant lipid blebs are evident. Potent ParE-mediated toxicity is also correlated with a hallmark signature of abortive DNA replication, consistent with the inhibition of DNA gyrase.

Keywords: DNA gyrase; DNA topology; ParE toxin; filamented morphology; toxin-antitoxin systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / genetics
  • Bacterial Toxins / toxicity
  • DNA Topoisomerase IV / biosynthesis*
  • DNA Topoisomerase IV / genetics
  • DNA Topoisomerase IV / toxicity*
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Gene Expression*
  • Mutagens / metabolism
  • Mutagens / toxicity
  • Nucleic Acid Conformation
  • Phenotype*
  • Proteobacteria / cytology
  • Proteobacteria / enzymology*
  • Proteobacteria / genetics
  • Time Factors

Substances

  • Bacterial Toxins
  • DNA, Bacterial
  • Mutagens
  • DNA Topoisomerase IV