Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Host Microbe. 2008 Dec 11;4(6):567-78. doi: 10.1016/j.chom.2008.11.001.

The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.

Author information

1
Department of Microbiology, Columbia University, New York, NY 10032, USA.

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.

Comment in

PMID:
19064257
PMCID:
PMC2646117
DOI:
10.1016/j.chom.2008.11.001
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center