Toxin-Antitoxin Systems

Toxin-antitoxin (TA) systems consist of a stable toxin that causes growth arrest or cell death by inhibiting essential cellular processes and a labile antitoxin, which counteracts the toxin. Initially, TA systems were described as a stabilization element of plasmids, but these two gene modules are also ubiquitous in prokaryotic genomes. When encoded on the genome, they often function as a regulatory switch that converts bacteria into persisters, a dormant state that is associated with increased antibiotic tolerance. We have recently identified several putative TA loci in the Gram-positive human pathogen Streptococcus pyogenes in a bioinformatics search. We aim to characterize these loci, elucidate the molecular mechanisms of these TA systems, and unravel their biological roles, including the triggers for activation of the toxins and their significance for persister cell formation.