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.
journal_name
Open Bioljournal_title
Open biologyauthors
Gopinath K,Venclovas C,Ioerger TR,Sacchettini JC,McKinney JD,Mizrahi V,Warner DFdoi
10.1098/rsob.120175subject
Has Abstractpub_date
2013-02-13 00:00:00pages
120175issue
2issn
2046-2441pii
rsob.120175journal_volume
3pub_type
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