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Chapter 23 : Pathogenic Mycobacteria
This chapter focuses on the information presently available about iron metabolism and its regulation in pathogenic mycobacteria; this information is derived mainly from experiments conducted with Mycobacterium tuberculosis. Mycobactins produced by different species vary mainly in the alkyl substitutions of the hydroxy acid and in the length of the acyl molecule, which varies between 10 and 21 carbons. The proteins encoded by the mbt cluster show significant homology to proteins involved in the biosynthesis of other structurally related siderophores such as yersiniabactin from Yersinia pestis and pyochelin from Pseudomonas aeruginosa. Disruption of the mbtB gene in M. tuberculosis results in loss of production of both mycobactin and carboxymycobactin, indicating a direct link between the mbt genes and siderophore synthesis. Carboxymycobactin is probably responsible for sequestering iron from transferrin in the phagosome, since normal release of iron from transferrin triggered by the acidic pH of the early endosome is reduced as a result of mycobacterium inhibition of phagosome acidification. A common characteristic of components of iron acquisition systems in prokaryotes and in higher organisms is that they are expressed only under conditions of iron limitation. Iron-dependent regulator (IdeR) is responsible for the differential expression of one-third of the M. tuberculosis genes whose expression is affected by iron availability.