management of dietary iron / tuberculosis
doe
Iron, mycobacteria and tuberculosis.
Ratledge C.
Department of Biological Sciences, University of Hull, Hull HU6 7RX, UK.
c.rat...@biosci.hull.ac.uk
The role of iron in the growth and metabolism of M. tuberculosis and other
mycobacteria is discussed in relation to the acquisiton of iron from host
sources, such as transferrin, lactoferrin and ferritin, and its subsequent
assimilation and utilization by the bacteria. Key components involved in the
acquisition of iron (as ferric ion) and its initial transport into the
mycobacterial cell are extracellular iron binding agents (siderophores) which,
in pathogenic mycobacteria, are the carboxymycobactins and, in saprophytic
mycobacteria, are the exochelins. In both cases, iron may be transferred to an
intra-envelope, short-term storage molecule, mycobactin. For transport across
the cell membrane, a reductase is used which converts FeIII-mycobactin to the
FeII form. The ferrous ion, possibly complexed with salicylic acid, is then
shuttled across the membrane either for direct incorporation into various
porphyrins and apoproteins or, for storage of iron within the bacterial
cytoplasm, bacterioferritin. The overall process of iron acquisition and its
utilization is under very genetic tight control. The importance of iron in the
virulence of mycobacteria is discussed in relationship to the development of
tuberculosis. The management of dietary iron can therefore be influential in
aiding the outcome of this disease. The role of the old anti-TB compound,
p-aminosalicylate (PAS), is discussed in its action as an inhibitor of iron
assimilation, together with the prospects of being able to synthesize further
selective inhibitors of iron metabolism that may be useful as future
chemotherapeutic agents.
Publication Types:
Review
Review, Tutorial
PMID: 14670352 [PubMed - indexed for MEDLINE]
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