Iron Metabolism in the Tubercle Bacillus and Other Mycobacteria

Abstract

The mechanism of iron acquisition by mycobacteria, and by the tubercle bacillus in particular, is one of the central issues concerning the pathogenicity of this group of bacteria. This chapter describes the key components of the iron acquisition system, how they interlink in the sequestration of iron from the host sources of iron, and how the iron is then made available to the bacterial cell for its own purposes. Mycobactins have been isolated from M. tuberculosis and most other mycobacteria, both pathogens and nonpathogens alike. The only exceptions would appear to be some (but not necessarily all) strains of M. paratuberculosis, M. vaccae, M. chelonae, M. parafortuium, and M. thermoresistible. Two different types of ferritins involved in iron storage have been identified, the heme-containing bacterioferritins and the heme-free ferritins. In contrast to the genes of bacterial iron acquisition systems, which are upregulated under low-iron conditions, the genes encoding iron storage proteins appear to be upregulated under high-iron conditions. Interestingly, the first mycobacterial bacterioferritins were identified during the characterization of immunodominant and highly expressed mycobacterial proteins in the early 1990s. When a person becomes infected with the tubercle bacillus or, indeed, other bacteria, one of the earliest defense mechanisms put into operation by the infected host is the withholding of iron from the invading bacteria by the transfer of all free iron into transferrin or lactoferrin, both of which deliberately have spare iron-binding capacity for this very purpose. This means that iron is automatically in limiting supply to the bacteria also.