Host biotin is required for liver stage development in malaria parasites
AuthorDellibovi-Ragheb, TA; Jhun, H; Goodman, CD; Walters, MS; Ragheb, DRT; Matthews, KA; Rajaram, K; Mishra, S; McFadden, GI; Sinnis, P; ...
Source TitleProceedings of the National Academy of Sciences of USA
PublisherNATL ACAD SCIENCES
AffiliationSchool of BioSciences
Document TypeJournal Article
CitationsDellibovi-Ragheb, T. A., Jhun, H., Goodman, C. D., Walters, M. S., Ragheb, D. R. T., Matthews, K. A., Rajaram, K., Mishra, S., McFadden, G. I., Sinnis, P. & Prigge, S. T. (2018). Host biotin is required for liver stage development in malaria parasites. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115 (11), pp.E2604-E2613. https://doi.org/10.1073/pnas.1800717115.
Access StatusOpen Access
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.
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