Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution

Vitamin B12 is required for normal human bodily functions and is not naturally produced in usable amounts by plants or fungi.

Mycobacterium tuberculosis no longer produces vitamin B12 on its own but can take it from the human host, unlike its ancestral relatives and environmental relatives that still make it; this change is linked to its ability to cause disease by relying on the host's vitamin B12.

Mycobacterium tuberculosis depends on vitamin B12 obtained from the host to cause severe infection, and without it, bacterial numbers decrease and survival improves in mice. Mycobacterium canettii, which produces its own vitamin B12, does not require host vitamin B12 to cause infection.

Mycobacterium tuberculosis becomes less able to cause disease when it cannot use vitamin B12 to make methionine via the MetH enzyme, and this effect depends on the availability of vitamin B12 in the host environment.

In Mycobacterium tuberculosis, a specific RNA structure that senses vitamin B12 turns off the metE gene when vitamin B12 is available. Mutations in this RNA structure prevent gene silencing and allow the bacteria to grow even when vitamin B12 is present.

Mycobacterium tuberculosis cannot absorb methionine from solid surfaces, whereas its ancestor Mycobacterium canettii and related environmental bacteria can still do so, showing that Mycobacterium tuberculosis has lost this metabolic function over time.