A vitamin B₁₂ transporter in Mycobacterium tuberculosis

Open Biol. 2013 Feb 13;3(2):120175. doi: 10.1098/rsob.120175.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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