Vitamin B12 metabolism in Mycobacterium tuberculosis

Mycobacterium tuberculosis is included among a select group of bacteria possessing the capacity for de novo biosynthesis of vitamin B-12, the largest and most complex natural organometallic cofactor. The bacillus is also able to scavenge B-12 and related corrinoids utilizing an ATP-binding cassette-type protein that is distinct from the only known bacterial B-12-specific transporter, BtuFCD. Consistent with the inferred requirement for vitamin B-12 for metabolic function, the M. tuberculosis genome encodes two B-12 riboswitches and three B-12-dependent enzymes. Two of these enzymes have been shown to operate in methionine biosynthesis (MetH) and propionate utilization (MutAB), while the function of the putative nrdZ-encoded ribonucleotide reductase remains unknown. Taken together, these observations suggest that M. tuberculosis has the capacity to regulate core metabolic functions according to B-12 availability - whether acquired via endogenous synthesis or through uptake from the host environment - and, therefore, imply that there is a role for vitamin B-12 in pathogenesis, which remains poorly understood.