The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites

Yu, Min; Kumar, T.R. Santha; Nkrumah, Louis J.; Coppi, Alida; Retzlaff, Silke; Li, Celeste D.; Kelly, Brendan J.; Moura, Pedro A.; Lakshmanan, Viswanathan; Freundlich, Joel S.; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H.-C.; Falkard, Brie; Sidhu, Amar bir Singh; Purcell, Lisa A.; Gratraud, Paul; Kremer, Laurent; Waters, Andrew P.; ... (2008). The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites. Cell host & microbe, 4(6), pp. 567-578. Cell Press 10.1016/j.chom.2008.11.001

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The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology
500 Science

ISSN:

1931-3128

Publisher:

Cell Press

Language:

English

Submitter:

Volker Heussler

Date Deposited:

01 Jun 2016 14:31

Last Modified:

02 Jun 2016 23:00

Publisher DOI:

10.1016/j.chom.2008.11.001

PubMed ID:

19064257

BORIS DOI:

10.7892/boris.81871

URI:

https://boris.unibe.ch/id/eprint/81871

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