A vitamin B?? transporter in Mycobacterium tuberculosis.

ABSTRACT: Vitamin B??-dependent enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B?? in vitro, it is uncertain whether the organism is able to scavenge B?? during host infection. This question is crucial to predictions of metabolic function, but its resolution is complicated by the absence in the M. tuberculosis genome of a direct homologue of BtuFCD, the only bacterial B?? transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B??. A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I)rrinoid adenosyltransferase as essential for B?? assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B?? acquisition for an ATP-binding cassette (ABC)-type protein previously investigated as the mycobacterial BacA homologue. Moreover, targeted deletion of Rv1819c eliminated the ability of M. tuberculosis to transport B?? and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B?? uptake in M. tuberculosis, and elucidate a role in B?? metabolism for an ABC protein implicated in chronic mycobacterial infection.

SUBMITTER: Gopinath K 

PROVIDER: S-EPMC3603451 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature