An NAD⁺ Phosphorylase Toxin Triggers Mycobacterium tuberculosis Cell Death.

ABSTRACT: Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 Å-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD⁺-dependent bacterial exotoxins, such as diphtheria toxin. Indeed, MbcT catalyzes NAD⁺ degradation in vitro and in vivo. Unexpectedly, the reaction is stimulated by inorganic phosphate, and our data reveal that MbcT is a NAD⁺ phosphorylase. In the absence of MbcA, MbcT triggers rapid M. tuberculosis cell death, which redu

SUBMITTER: Freire DM 

PROVIDER: S-EPMC6436930 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature