Bacterial Type I Toxins: Folding and Membrane Interactions

Toxins (Basel). 2021 Jul 14;13(7):490. doi: 10.3390/toxins13070490.


Bacterial type I toxin-antitoxin systems are two-component genetic modules that encode a stable toxic protein whose ectopic overexpression can lead to growth arrest or cell death, and an unstable RNA antitoxin that inhibits toxin translation during growth. These systems are widely spread among bacterial species. Type I antitoxins are cis- or trans-encoded antisense small RNAs that interact with toxin-encoding mRNAs by pairing, thereby inhibiting toxin mRNA translation and/or inducing its degradation. Under environmental stress conditions, the up-regulation of the toxin and/or the antitoxin degradation by specific RNases promote toxin translation. Most type I toxins are small hydrophobic peptides with a predicted α-helical transmembrane domain that induces membrane depolarization and/or permeabilization followed by a decrease of intracellular ATP, leading to plasmid maintenance, growth adaptation to environmental stresses, or persister cell formation. In this review, we describe the current state of the art on the folding and the membrane interactions of these membrane-associated type I toxins from either Gram-negative or Gram-positive bacteria and establish a chronology of their toxic effects on the bacterial cell. This review also includes novel structural results obtained by NMR concerning the sprG1-encoded membrane peptides that belong to the sprG1/SprF1 type I TA system expressed in Staphylococcus aureus and discusses the putative membrane interactions allowing the lysis of competing bacteria and host cells.

Keywords: folding; mechanisms of action; membrane depolarization; membrane permeabilization; nucleoid condensation; pore formation; structure; toxin-antitoxin systems; type I toxins.

Publication types

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

MeSH terms

  • Antitoxins / genetics
  • Bacteria / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Toxins / genetics
  • Bacterial Toxins / toxicity*
  • Gene Expression Regulation, Bacterial
  • Gram-Positive Bacteria
  • RNA, Bacterial / genetics
  • RNA, Messenger / metabolism
  • Ribonucleases / genetics
  • Staphylococcal Infections
  • Staphylococcus aureus / genetics
  • Toxin-Antitoxin Systems / genetics


  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • RNA, Bacterial
  • RNA, Messenger
  • Ribonucleases