Investigating heme uptake in mycobacteria

Abstract

Iron is an essential element for all forms of life. Pathogens, such as Mycobacterium tuberculosis, must acquire iron from their host in order to survive. While M. tuberculosis has been shown to uptake host transferrin iron via a siderophore‐mediated mechanism, our laboratory has identified a unique heme uptake pathway in mycobacteria. Here, M. smegmatis is used as a model system to determine the genomic region proposed to be responsible for heme uptake. Thus far, we have deleted a particular region containing seven genes and this mutant only grew in iron supplemented media and not heme. We then complemented our heme uptake mutant with the corresponding genes in M. tuberculosis, and showed that the complementation restored growth in heme supplemented media. Hence, we have identified the genomic region responsible for heme uptake in M. tuberculosis. Additionally, we will present biochemical analyses of the putative hemophore and extracellular domains of MmpL11, a proposed heme transporter, and the possible pathway of transfer of heme from protein to another.