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Iron metabolism in trypanosomatids, and its crucial role in infection

Published online by Cambridge University Press:  15 February 2010

M. C. TAYLOR  and
J. M. KELLY
M. C. TAYLOR*
Affiliation:
Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
J. M. KELLY
Affiliation:
Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
*
*Corresponding author: Tel: 0044 207 927 2615. Fax: 0044 207 636 8739. E-mail: martin.c.taylor@lshtm.ac.uk
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Summary

Iron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals – a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental to Trypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention.

Keywords

TrypanosomaLeishmaniairon transporttransferrinanaemiasuperoxide dismutase

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Type
Review Article
Information
Parasitology , Volume 137 , Issue 6 , May 2010 , pp. 899 - 917
Copyright
Copyright © Cambridge University Press 2010

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