Identification of the Thioredoxin Partner of Vitamin K Epoxide Reductase in Mycobacterial Disulfide Bond Formation

Disulfide bond formation has a great impact on bacterial pathogenicity. Thus, disulfide-bond-forming proteins represent new targets for the development of antibacterials, since the inhibition of disulfide bond formation would result in the simultaneous loss of the activity of several classes of virulence factors. Here, we identified five candidate proteins encoded by theM. tuberculosis genome as possible substrates of theM. tuberculosis VKOR protein involved in disulfide bond formation. We then reconstituted the mycobacterial disulfide bond formation pathway inE. coli and showed that of the five candidates, onlyM. tuberculosis DsbA is efficiently oxidized by VKOR inE. coli . We also present evidence for the involvement of VKOR in DsbA oxidation inM. smegmatis .