Abstract
The regulation of metal ion concentrations is central to the physiology of the interaction between pathogenic bacteria and their hosts. Apart from the NRAMP orthologue, MntH, metal ion transporters in Mycobacterium tuberculosis have not been studied. Mn, the physiological substrate of MntH in other bacteria, may play an important role as a structural and redox-active cofactor in a wide range of metabolic processes. Fe, Cu and Zn play structural and catalytic roles in metalloenzymes involved in oxidative stress responses. Fe and Mg are required for growth in macrophages. Genomic analyses reveal 28 sequences encoding a broad repertoire of putative metal ion transporters (or transporter subunits), representing 24% of all transporters in this organism. These comprise 8 families of secondary active transporters and 3 families of primary active transporters, including 12,P, type ATPases. Potential metal ion specificities include K+, Na+, Cu2+, Cd2+, Zn2+, Mn2+, Mg2+, Ca2+, Co2+, Ni2+, Fe2+/3+, Hg2+, AsO2- and AsO4(2-). 17 of these transporters are also encoded as complete open reading frames in Mycobacterium leprae, suggesting a role in intracellular survival. Iron transcriptionally regulates a diverse set of genes via the iron-depen...Continue Reading
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