Iron Acquisition and Metabolism by Mycobacteria

Abstract

Iron is an obligate cofactor for at least 40 different enzymes encoded in the Mycobacterium tuberculosis genome (8). It is required for the cytochromes involved in electron transport and other hemoproteins involved in oxygen metabolism, such as catalase-peroxidase KatG. Most of the intracellular iron in mycobacteria, however, is in the form of nonheme iron (48). One important form of nonheme iron is the iron-sulfur clusters that are cofactors of proteins involved in amino acid and pyrimidine biogenesis, as well as in enzymes involved in the tricarboxylic acid cycle and electron transport. Iron is also required for DNA synthesis in ribonucleotide reductase, superoxide dismutase, and 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (Rv2178c; DAHP synthase [Every gene in the genome of M. tuberculosis H37Rv has been assigned a gene identifier beginning with Rv which can be used to retrieve information on line; see reference 30a]). It has been estimated that 7 to 64 μg of Fe/g of mycobacterial cell mass is required to support growth (39, 48). Iron limitation in vitro to levels below these can result in growth restriction in many species of mycobacteria, including pathogens such as M. tuberculosis. Since iron is the fourth most abundant element, difficulty in its acquisition may seem counterintuitive. However, the extremely low solubility of ferric ion in aqueous solution makes obtaining it difficult and so microorganisms have evolved many strategies for acquiring sufficient soluble iron for aerobic growth.