Recent insights into fatty acid acquisition and metabolism in malarial parasites

F1000 Biology Reports 03/2010; 2(1). DOI: 10.3410/B2-24
Source: PubMed


The malarial parasite has a tremendous requirement for fatty acids during the replicative stages that take place in the mammalian host. A series of recent papers, discussed below, have revealed some of the mechanisms employed by the parasite to meet these demands.

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    • "In P. falciparum, it maintains a 35-kb circular genome and several particular biochemical pathways that are present in bacteria and plants but are absent in humans, thus providing many attractive targets that are extensively investigated for drug development. These pathways include the type II fatty acid biosynthesis pathway, which involves 6 distinct enzymes in Plasmodium while in human the type I fatty acid biosynthesis pathway involves a multifunctional enzyme, the 1- deoxy D xylulose 5 phosphate (DOXP) isoprenoid biosynthesis pathway that is mevalonateindependent in the malaria parasite contrary to humans, and apicoplast replication, transcription and translation which involve enzymes of bacterial origins (Dahl & Rosenthal, 2008, Goodman & McFadden, 2007, Grawert et al., 2011, Jayabalasingham et al., 2010). "

    Full-text · Chapter · Mar 2012
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    Full-text · Chapter · Mar 2012
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    ABSTRACT: Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Ɛ4, Ɛ3 and Ɛ2 with APOE Ɛ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Ɛ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Ɛ4 children for Plasmodium spp. densities compared to non-APOE Ɛ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Ɛ4 allele compared to those without an APOE Ɛ4 allele. When considering non-APOE Ɛ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Ɛ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Ɛ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Ɛ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.
    Full-text · Article · Oct 2013 · PLoS ONE
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