A vitamin B₁₂ transporter in Mycobacterium tuberculosis.

Abstract

Vitamin B₁₂-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 B₁₂ in vitro, it is uncertain whether the organism is able to scavenge B₁₂ 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 B₁₂ transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B₁₂. A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I)rrinoid adenosyltransferase as essential for B₁₂ assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B₁₂ 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 B₁₂ and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B₁₂ uptake in M. tuberculosis, and elucidate a role in B₁₂ metabolism for an ABC protein implicated in chronic mycobacterial infection.

• Authors: Krishnamoorthy Gopinath, Ceslovas Venclovas, Thomas R Ioerger, James C Sacchettini, John D McKinney, Valerie Mizrahi, Digby F Warner
• Journal: Open biology (Open Biol) Vol. 3 Issue 2 Pg. 120175 (Feb 13 2013) ISSN: 2046-2441 [Electronic] England
• PMID: 23407640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• DNA Transposable Elements
• Vitamin B 12

Topics

• ATP-Binding Cassette Transporters (genetics, metabolism)
• Biological Transport
• DNA Transposable Elements (genetics)
• Genome, Bacterial (drug effects)
• Host-Pathogen Interactions (genetics)
• Humans
• Mutagenesis
• Mutation
• Mycobacterium Infections (metabolism, microbiology)
• Mycobacterium tuberculosis (drug effects, genetics, metabolism, pathogenicity)
• Vitamin B 12 (metabolism, pharmacology)