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Host biotin is required for liver stage development in malaria parasites.


ABSTRACT: 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.

SUBMITTER: Dellibovi-Ragheb TA 

PROVIDER: S-EPMC5856565 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Host biotin is required for liver stage development in malaria parasites.

Dellibovi-Ragheb Teegan A TA   Jhun Hugo H   Goodman Christopher D CD   Walters Maroya S MS   Ragheb Daniel R T DRT   Matthews Krista A KA   Rajaram Krithika K   Mishra Satish S   McFadden Geoffrey I GI   Sinnis Photini P   Prigge Sean T ST  

Proceedings of the National Academy of Sciences of the United States of America 20180226 11


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 biotinyla  ...[more]

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