Toxin/antitoxin systems influence biofilm and persister cell formation and the general stress response

In many genomes, toxin-antitoxin (TA) systems have been identified; however, their role in cell physiology has been unclear. Here we examine the evidence that TA systems are involved in biofilm formation and persister cell formation and that these systems may be important regulators of the switch from the planktonic to the biofilm lifestyle as a stress response by their control of secondary messenger 3,5-cyclic diguanylic acid. Specifically, upon stress, the sequence-specific mRNA interferases MqsR and MazF mediate cell survival. In addition, we propose that TA systems are not redundant, as they may have developed to respond to specific stresses. Toxin-antitoxin (TA) systems typically consist of two genes in an operon which encode a stable toxin that disrupts an essential cellular process (e.g., translation via mRNA degrada-tion) and a labile antitoxin (either RNA or a protein) that prevents toxicity (73). RNA antitoxins are known as type I if they inhibit toxin translation as antisense RNA or type III if they inhibit toxin activity; type II antitoxins are proteins that inhibit toxin activity (48). For type II systems (Fig. 1), th