ClpXP-mediated Degradation of the TAC Antitoxin is Neutralized by the SecB-like Chaperone in Mycobacterium tuberculosis

Bacterial toxin-antitoxin (TA) systems are composed of a deleterious toxin and its antagonistic antitoxin. They are widespread in bacterial genomes and mobile genetic elements, and their functions remain largely unknown. Some TA systems, known as TAC modules, include a cognate SecB-like chaperone that assists the antitoxin in toxin inhibition. Here, we have investigated the involvement of proteases in the activation cycle of the TAC system of the human pathogen Mycobacterium tuberculosis. We show that the deletion of endogenous AAA(+) proteases significantly bypasses the need for a dedicated chaperone and identify the mycobacterial ClpXP1 P2 complex as the main protease involved in TAC antitoxin degradation. In addition, we show that the ClpXP1 P2 degron is located at the extreme C-terminal end of the chaperone addiction (ChAD) region of the antitoxin, demonstrating that ChAD functions as a hub for both chaperone binding and recognition by proteases. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Bacterial toxin-antitoxin systems, including TAC modules with SecB-like chaperones, are widespread in bacterial genomes. Deletion of endogenous AAA(+) proteases bypasses the need for a dedicated chaperone, and the ClpXP1 P2 complex is identified as the main protease involved in TAC antitoxin degradation.