@article{91d97b0141ac49a98e46f630bd65de8c,
title = "The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites",
abstract = "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.",
keywords = "CHEMBIO, MICROBIO",
author = "Min Yu and Kumar, {T. R.Santha} and Nkrumah, {Louis J.} and Alida Coppi and Silke Retzlaff and Li, {Celeste D.} and Kelly, {Brendan J.} and Moura, {Pedro A.} and Viswanathan Lakshmanan and Freundlich, {Joel S.} and Valderramos, {Juan Carlos} and Catherine Vilcheze and Mark Siedner and Tsai, {Jennifer H.C.} and Brie Falkard and Sidhu, {Amar bir Singh} and Purcell, {Lisa A.} and Paul Gratraud and Laurent Kremer and Waters, {Andrew P.} and Guy Schiehser and Jacobus, {David P.} and Janse, {Chris J.} and Arba Ager and Jacobs, {William R.} and Sacchettini, {James C.} and Volker Heussler and Photini Sinnis and Fidock, {David A.}",
note = "Funding Information: We thank Drs. Geoff McFadden and Anthony Holder for the P. falciparum ACP and P. yoelii MSP1 antibodies and the Fidock lab members for helpful discussions. PfERD2 rabbit antiserum (MRA-1) was obtained through the MR4, deposited by John Adams. This work was supported by the National Institutes of Health (P01 AI060342, J.C.S., D.A.F., and W.R.J.; and R01 AI056840, P.S.), the Medicines for Malaria Venture (D.A.F., J.C.S., W.R.J., and D.A.J.), the Robert A. Welch Foundation (J.C.S.), the Deutsche Forschungsgesellschaft (DFG) (4497/1-2, V.H.), the Minist{\`e}re de l'Education Nationale de la Recherche et des Technologies (P.G.), and the Centre National de la Recherche Scientifique (L.K.). The authors all declare no conflict of interests. ",
year = "2008",
month = dec,
day = "11",
doi = "10.1016/j.chom.2008.11.001",
language = "English (US)",
volume = "4",
pages = "567--578",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}