Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology

Mol Cell. 2018 Jun 7;70(5):768-784. doi: 10.1016/j.molcel.2018.01.003. Epub 2018 Feb 3.

Abstract

Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules.

Keywords: RNA biology; abortive infection; antibiotic tolerance; bacterial persistence; conditional cooperativity; plasmid addiction; post-segregational killing; toxin-antitoxin modules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitoxins / chemistry
  • Antitoxins / genetics
  • Antitoxins / metabolism*
  • Bacteria / genetics
  • Bacteria / immunology
  • Bacteria / metabolism*
  • Bacteria / pathogenicity
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Drug Resistance, Bacterial / genetics
  • Evolution, Molecular
  • Gene Expression Regulation, Bacterial
  • Immunity, Innate
  • Microbial Viability
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • RNA Processing, Post-Transcriptional
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism*
  • Structure-Activity Relationship
  • Transcription, Genetic

Substances

  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • RNA, Bacterial