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

Abstract

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.

Fig. 1.

Type II toxin-antitoxin systems. Type II TA systems are typically transcribed in the same operon with the antitoxin gene preceding the toxin gene (although there are exceptions, such as mqsRA). Transcription of the two genes is generally autoregulated by the toxin-antitoxin complex. Proteases Lon, ClpAP, and ClpXP usually degrade labile protein antitoxins and liberate the toxin. Activated toxins function as endoribonucleases or gyrase inhibitors.

Fig. 2.

Schematic of how toxicity is mediated by mRNA interferases MqsR, MazF, YafQ, and ChpB. Toxin-antitoxin systems are induced by various environmental stresses (indicated by lightning bolts) (Table 1) which serve to induce proteases such as Lon that degrade antitoxins. Upon degradation of the antitoxin, the free toxin cleaves most cellular mRNAs in a sequence-specific manner. This leads to reduced production of large proteins (encoded by mRNAs with cleavage sites shown in black) and an enrichment of small proteins (encoded by mRNAs that lack cleavage sites and shown in orange for MazF, blue for MqsR, green for ChpB, and purple for YafQ) that are death proteins or stress proteins (which help the cell cope with the stress). Cellular mRNAs that contain cleavage sites for each toxin but remain uncleaved are marked with an accessory protein (in brown); these mRNAs may also be protected by secondary structure. The roles of YafQ and ChpB in determining the fate of the cells need to be investigated further.