Toxin-Antitoxin Loci in Mycobacterium tuberculosis

Abstract

Chromosomally encoded type II toxin–antitoxin (TA) systems generally consist of two adjacent genes in an operon encoding a stable toxin and a less stable, protease-sensitive cognate antitoxin. While the toxin and the antitoxin form a stable complex under normal growth conditions, the degradation of the antitoxin by stress-proteases under certain conditions leads to activation of the toxin and subsequent growth inhibition. Such stress-responsive TA systems have been associated with various cellular processes, including stabilization of genomic regions, protection against foreign DNA, biofilm formation, persistence, and control of the stress response. Yet, the contribution of chromosomal TA to bacterial virulence is presently unknown. Herein, we investigate the potential role of multiple chromosomally encoded TA systems in virulence, focusing on the tuberculosis agent Mycobacterium tuberculosis, which contains more than 70 TA loci in its genome. We describe what is currently known about the multiple TA families present in this bacterium, with emphasis on the recently discovered atypical stress-responsive toxin–antitoxin-chaperone (TAC) system, a TA system controlled by a SecB-like chaperone.