ReviewPost-screenDrug targeting of heme proteins in Mycobacterium tuberculosis

- Mycobacterium tuberculosis causes more deaths than any other infectious disease.
- Heme-binding enzymes are crucial for M. tuberculosis survival in its human host.
- Targeting essential M. tuberculosis hemoproteins can provide new TB therapeutics.
- Inhibitors of several M. tuberculosis heme enzymes have already been developed.
- P450s, heme transporters and heme oxygenases are among important new TB targets.

TB, caused by the human pathogen Mycobacterium tuberculosis (Mtb), causes more deaths than any other infectious disease. Iron is crucial for Mtb to infect the host and to sustain infection, with Mtb encoding large numbers of iron-binding proteins. Many of these are hemoproteins with key roles, including defense against oxidative stress, cellular signaling and regulation, host cholesterol metabolism, and respiratory processes. Various heme enzymes in Mtb are validated drug targets and/or products of genes essential for bacterial viability or survival in the host. Here, we review the structure, function, and druggability of key Mtb heme enzymes and strategies used for their inhibition.