Malaria, a disease caused by protozoan parasites, is one of the most dangerous infectious diseases, claiming millions of lives and infecting hundreds of millions of people annually. Malaria parasites contain an essential organelle called the apicoplast that is thought to have arisen through endosymbiosis of an algal cell which had previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that differ significantly from those of the human host. We are investigating biochemical pathways found in the apicoplast, particularly those required for the biosynthesis and modification of fatty acids. This metabolism should require several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters. We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of blood stage or liver stage malaria parasites. We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
Dellibovi-Ragheb TA, Jhun H, Goodman CD, Walters MS, Ragheb DRT, Matthews KA, Rajaram K, Mishra S, McFadden GI, Sinnis P, Prigge ST. Host biotin is required for liver stage development in malaria parasites. Proc Natl Acad Sci U S A. 2018 PubMed PMID: 29483266.
Afanador GA, Guerra AJ, Swift RP, Rodriguez RE, Bartee D, Matthews KA, Schon A, Freire E, Freel Meyers CL, Prigge ST. A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species. Mol Microbiol. 2017 PMID: 28836704.
Guerra AJ, Afanador GA, Prigge ST. Crystal structure of lipoate-bound lipoate ligase 1, LipL1, from Plasmodium falciparum. Proteins. 2017 PMID: 28543853.
Afanador GA, Matthews KA, Bartee D, Gisselberg JE, Walters MS, Freel Meyers CL, Prigge ST. Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. Mol Microbiol. 2014 PMID: 25116855.
Gisselberg JE, Dellibovi-Ragheb TA, Matthews KA, Bosch G, Prigge ST. The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS Pathog. 2013 PMID: 24086138.