"The coordination of heme uptake and synthesis in mycobacteria" by Rebecca Donegan

Iron is necessary for the survival of most pathogens. In the human host, iron is extremely limited and the vast majority of bioavailable iron is found as heme-iron. Infectious mycobacteria, like Mycobacterium tuberculosis (Mtb), have evolved pathways to use heme from the host as an iron source. Mtb can also synthesize heme de novo, and since heme is both necessary and cytotoxic, Mtb must regulate uptake and synthesis to maintain heme homeostasis, however how Mtb regulates heme uptake and whether host derived heme can be utilized directly by Mtb is not known. Our work shows that, the terminal heme synthesis enzyme in Mtb, coproheme decarboxylase (ChdC), has a second role in coordinating heme uptake in both Mtb and the nontuberculous mycobacterium, Mycobacterium smegmatis (Msm). Furthermore, we have found that ChdC expression is regulated in an iron dependent manner, suggesting a role for ChdC in regulating heme uptake in response to iron availability. The regulation of heme uptake by ChdC may be important for survival of mycobacteria in the host and could prove a useful target for anti-mycobacterial drugs.