TAC from Mycobacterium tuberculosis: a paradigm for stress-responsive toxin-antitoxin systems controlled by SecB-like chaperones

Bacterial type II toxin-antitoxins (TAs) are two-component systems that modulate growth in response to specific stress conditions, thus promoting adaptation and persistence. The major human pathogen Mycobacterium tuberculosis potentially encodes 75 TAs and it has been proposed that persistence induced by active toxins might be relevant for its pathogenesis. In this work, we focus on the newly discovered toxin-antitoxin-chaperone (TAC) system of M. tuberculosis, an atypical stress-responsive TA system tightly controlled by a molecular chaperone that shows similarity to the canonical SecB chaperone involved in Sec-dependent protein export in Gram-negative bacteria. We performed a large-scale genome screening to reconstruct the evolutionary history of TAC systems and found that TAC is not restricted to mycobacteria and seems to have disseminated in diverse taxonomic groups by horizontal gene transfer. Our results suggest that TAC chaperones are evolutionary related to the solitary chaperone SecB and have diverged to become specialized toward their cognate antitoxins.