Make It or Take It: Fatty Acid Metabolism of Apicomplexan Parasites

Abstract

Lipids are essential and highly abundant components of all organisms. They serve as the main building blocks of the mem- branes that surround and compartmentalize cells, as a store for energy and reduction power, and in posttranslational modifi- cations that regulate the localization and function of a large number of proteins. Lipids have also emerged as important pathogenesis factors in a variety of infectious diseases. The ability to synthesize or salvage simple components like fatty acids and isoprenoids and assemble them into more complex molecules is critical for the growth and development of the pathogen and required for its ability to colonize the host and to cause disease. Here we will focus on the fatty acid metabolism of apicomplexans, a group of unicellular eukaryotes that have adapted to an obligate intracellular life style. Infections with apicomplexan parasites are the cause of several important hu- man diseases (malaria, toxoplasmosis, and cryptosporidiosis) affecting literally millions of people around the globe. Control efforts for these diseases face an uphill battle, as effective vaccines are lacking for any of these parasites and drug treat- ment is not fully effective (cryptosporidiosis), limited to the acute stage (toxoplasmosis), or constantly threatened by emerging drug resistance (malaria). The completion of full genome sequencing efforts for a considerable number of api- complexans has reinvigorated the search for targets of novel therapeutics. Lipid and fatty acid metabolism has emerged at the heart of several intensively studied areas of apicomplexan biology, including parasite adaptation to different hosts, host- parasite interaction at the cellular level, and the identification of divergent pathogen-specific targets for antiparasitic drug therapy. Here we will provide an overview of the surprisingly diverse mechanisms of fatty acid synthesis (FAS) and uptake used by the members of this important group of pathogens. MAKE IT I: THE APICOPLAST TYPE II FATTY ACID SYNTHESIS PATHWAY