Sean Prigge is a professor with the Department of Molecular Microbiology and Immunology. His research focuses on enzymes and metabolic pathways in malaria parasites.
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 malaria parasites. We approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
Afanador, G.A., K.A. Matthews, D. Bartee, J.E. Gisselberg, M.S. Walters, C.L. Freel Meyers, and S.T. Prigge. (2014) Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum, Mol Microbiol 94, 156-171.
Afanador, G.A., S.P. Muench, M. McPhillie, A. Fomovska, A. Schon, Y. Zhou, G. Cheng, J. Stec, J.S. Freundlich, H.M. Shieh, J.W. Anderson, D.P. Jacobus, D.A. Fidock, A.P. Kozikowski, C.W. Fishwick, D.W. Rice, E. Freire, R. McLeod, and S.T. Prigge. (2013) Discrimination of Potent Inhibitors of Toxoplasma gondii Enoyl-Acyl Carrier Protein Reductase by a Thermal Shift Assay, Biochemistry 52, 9155-9166.
Gisselberg, J.E., T.A. Dellibovi-Ragheb, K.A. Matthews, G. Bosch, and S.T. Prigge. (2013) The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites, PLoS Pathog 9, e1003655.
Delli-Bovi, T.A., J.E. Gisselberg and S.T. Prigge. (2013) Parasites FeS up: iron-sulfur cluster biogenesis in eukaryotic pathogens. PLoS Pathog. 9(4):e1003227.
Falkard, B., C. Deschermeier, L.-S. Hecht, K.A. Mathews, T.R.S. Kumar, A. Ecker, P. Sinnis, S.T. Prigge, V. Heussler and D.A. Fidock. (2013) A key role for lipoic acid synthesis during plasmodium liver-stage development. Cell. Microbiol. 15:1585-1604.
Fomovska, A., Q. Huang, K. El Bissati, E.J. Mui, W.H. Witola, G. Cheng, T. Zhou, C. Sommerville, C.W. Roberts, S. Bettis, S.T. Prigge, G.A. Afanador, M.R. Hickman, P.J. Lee, S.E. Leed, J.M. Auschwitz, M. Pieroni, J. Stec, S.P. Muench, D.W. Rice, A.P. Kozikowski, and R. McLeod. (2012) Novel N-benzoyl-2-hydroxybenzamide disrupts unique parasite secretory pathway. Antimicrob. Agents Chemother. 56:2666-2682.
Gallagher, J.R., K.A. Matthews, and S.T. Prigge. (2011) Plasmodium falciparum apicoplast transit peptides are unstructured in vitro and during apicoplast import. Traffic 9:1124-1138.
Bankeu, J.J., R. Khayala, B.N. Lenta, D.T. Noungoué, S.A. Ngouela, S.A. Mustafa, K. Asaad, M.I. Choudhary, S.T. Prigge, R. Hasanov, A.E. Nkengfack, E. Tsamo, and M.S. Ali. (2011) Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso. J. Nat. Prod. 74:1370-1378.
Chufán, E.E., S.T. Prigge, X. Siebert, B.A. Eipper, R.E. Mains, and L.M. Amzel. (2010) Differential reactivity between two copper sites in peptidylglycine alpha-hydroxylating monooxygenase. J. Am. Chem. Soc. 132:15565-15572.
Delli-Bovi, T.A., M.D. Spalding, and S.T. Prigge. (2010) Overexpression of biotin synthase and biotin ligase is required for efficient generation of sulfur-35 labeled biotin in E. Coli. BMC Biotechnol. 10:73.
Spalding, M.D., and S.T. Prigge. (2010) Lipoic acid metabolism in microbial pathogens. Microbiol. Mol. Biol. Rev. 74:200-228.
Spalding, M.D., M. Allary, J.R. Gallagher, and S.T. Prigge. (2010) Validation of a modified method for Bxb1 mycobacteriophage integrase-mediated recombination in Plasmodium falciparum by localization of the H-protein of the glycine cleavage complex to the mitochondrion. Mol. Biochem. Parasit. 172:156-160.
Du, Y., J.E. Gisselberg, J.D. Johnson, P.J. Lee, S.T. Prigge, and B.O. Bachmann. (2010) Lactococcus lactis FabH, encoding ß-Ketoacyl-ACP synthase, can be functionally replaced by the Plasmodium falciparum congener. Appl. Env. Microbiol. 76:3959:3966.
Gallagher, J.R., and S.T. Prigge. (2009) Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth. Proteins: Struc. Func. Bioinf. 78:575-588.
Spalding, M.D., and S.T. Prigge. (2009) The amidase domain of lipoamidase specifically inactivates lipoylated proteins in vivo. PLoS One 4:e7394.
Lee, P.J., J.B. Bhonsle, H.W. Gaona, D.P. Huddler, T.N. Heady, M. Kreishman-Deitrick, A. Bhattacharjee, W.F. McCalmont, L. Gerena, M. Lopez-Sanchez, N.E. Roncal, T.H. Hudson, J.D. Johnson, S.T. Prigge, and N.C. Waters. (2009) Targeting the fatty acid biosynthesis enzyme, PfKASIII, in the identification of novel antimalarial agents. J. Med. Chem. 52:952-963.
Lu, J.L., S.P. Muench, M. Allary, S.A. Campbell, C.W. Roberts, E. Mui, R.L. McLeod, D.W. Rice, and S.T. Prigge. (2007) Type I and type II fatty acid biosynthesis in Eimeria tenella: Enoyl reductase activity and structure. Parasitology 134:1949-1962.