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

Yu, M. et al. (2008) The fatty acid biosynthesis enzyme fabi plays a key role in the development of liver stage malarial parasites. Cell Host and Microbe, 4(6), pp. 567-568. (doi: 10.1016/j.chom.2008.11.001)

Abstract

The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in <i>Plasmodium falciparum</i> asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes Fab1. Here, we report synthetic chemistry and transfection studies concluding that <i>Plasmodium</i> Fab1 is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial Fab1. Disruption of <i>fab1</i> in <i>P. falciparum</i> or the rodent parasite <i>P. berghei</i> does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient <i>P. berghei</i> sporozoites are markedly less infective for mice and typically fail to complete liver-stage development invitro. 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: Articles
• Keywords: microbio, chembio
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Waters, Professor Andy
• Authors: Yu, M., Kumar, T.R.S., Nkrumah, L.J., Coppi, A., Retzlaff, S., Li, C.D., Kelly, B.J., Moura, P.A., Lakshmanan, V., Freundlich, J.S., Valderramos, J.C., Vilcheze, C., Siedner, M., Tsai, J. H., Flkard, B., Sidhu, A.B., Purcell, L.A., Gratraud, P., Kremer, L., Waters, A.P., Schieser, G., Jacobus, D.P., Janse, C.J., Ager, A., Jacobs, W.R., Sachettini, J.C., Heussler, V., Sinnis, P., and Fidock, D.A.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry; Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cell Host and Microbe
• ISSN: 1931-3128
• Published Online: 10 December 2008