The virulence of Mycobacterium tuberculosis requires its capacity to scavenge host vitamin B12 for methionine synthesis through the MetH enzyme, as deletion of metE reduces virulence primarily under low vitamin B12 conditions, while deletion of metH reduces virulence only under normal vitamin B12 conditions due to riboswitch-mediated repression of metE.

Mycobacterium tuberculosis steals vitamin B12 from the host to power a key enzyme that makes methionine, an essential building block for proteins. When B12 is plentiful, the bacterium shuts down its backup enzyme and relies entirely on the B12-powered one. If B12 runs low, the backup enzyme turns on, but it is less efficient. If either enzyme is broken, the bacterium cannot make enough methionine and cannot grow properly in the host. This dependency exists because the bacterium lost its ability to make B12 over time, forcing it to rely entirely on the host.