Cryptosporidium parvum is a unicellular pathogen that can cause severe watery diarrhea in humans and animals. This pathogen can cause one of the opportunistic infections in AIDS patients for which no complete effective treatment is yet available. Cryptosporidium is also a significant water- and food-borne pathogen, and listed as one of the Category B priority pathogens in the NIH biodefense research program. The slow development of anti-cryptosporidiosis chemotherapy is primarily due to the poor understanding on the basic metabolic pathways in this parasite. Many well-defined or promising drug targets found in other apicomplexans are either absent or highly divergent in C. parvum. Therefore, detailed molecular and functional studies on the unique C. parvum metabolic pathways are needed for the understanding and control of this parasite. Fatty acids are one of the essential components in all cells. We have pioneered the research on the fatty acid synthesis in C. parvum. Our current data have revealed that C. parvum differs from other apicomplexans by lacking Type II FAS and its associated apicoplast, and relying on three distinct pathway for elongating fatty acids (ie. a Type I modular fatty acid synthase (CpFASI), a polyketide synthase (CpPKSI), and a long chain fatty acyl elongase (CpLCEl). In addition, we have identified putative major components that constitute the highly streamlined fatty acid metabolism in C.parvum. These advances now allow us to rationally dissect the function of C. parvum fatty acid metabolism in detail. Our long-term goal is to delineate the function(s) of major components constituting the fatty acid metabolism in C. parvum and to explore this pathway as a rational drug target. Our hypothesis is that major enzymes involved in the C. parvum fatty acid metabolism differ from their counterparts in humans and animals at both structural and functional levels, and may serve as rational drug targets. In this proposal, we will focus on studying different mechanisms governing fatty acid elongation and activation in C. parvum by achieving the following three specific aims: 1) To delineate the molecular machineries governing the fatty acid synthesis in the parasite by functional analyses of CpFASI, CpPKS! and a membrane-associated fatty acid elongase. 2) To elucidate the molecular mechanisms involved in the activation and transporting of fatty acids by functional analyses of acyl-CoA synthases and fatty acyl-CoA binding protein. 3) To validate that fatty acid metabolic enzymes may serve as rational drug target in Cryptosporidium by discovering inhibitors selectively against, parasite fatty acid metabolic enzymes.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
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Rogers, Martin J
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Texas Agrilife Research
Other Basic Sciences
Schools of Earth Sciences/Natur
College Station
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Guo, Fengguang; Zhang, Haili; Payne, Harold Ross et al. (2016) Differential Gene Expression and Protein Localization of Cryptosporidium parvum Fatty Acyl-CoA Synthetase Isoforms. J Eukaryot Microbiol 63:233-46
Guo, Fengguang; Zhang, Haili; Fritzler, Jason M et al. (2014) Amelioration of Cryptosporidium parvum infection in vitro and in vivo by targeting parasite fatty acyl-coenzyme A synthetases. J Infect Dis 209:1279-87
Fritzler, Jason M; Zhu, Guan (2012) Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP). J Antimicrob Chemother 67:609-17
Guo, Fengguang; Zhu, Guan (2012) Presence and removal of a contaminating NADH oxidation activity in recombinant maltose-binding protein fusion proteins expressed in Escherichia coli. Biotechniques 52:247-53
Zhu, Guan; Shi, Xiangyu; Cai, Xiaomin (2010) The reductase domain in a Type I fatty acid synthase from the apicomplexan Cryptosporidium parvum: restricted substrate preference towards very long chain fatty acyl thioesters. BMC Biochem 11:46
Yu, Yonglan; Zhang, Haili; Zhu, Guan (2010) Plant-type trehalose synthetic pathway in cryptosporidium and some other apicomplexans. PLoS One 5:e12593
Templeton, Thomas J; Enomoto, Shinichiro; Chen, Wei-June et al. (2010) A genome-sequence survey for Ascogregarina taiwanensis supports evolutionary affiliation but metabolic diversity between a Gregarine and Cryptosporidium. Mol Biol Evol 27:235-48
Lei, Cheng; Rider Jr, S Dean; Wang, Cai et al. (2010) The apicomplexan Cryptosporidium parvum possesses a single mitochondrial-type ferredoxin and ferredoxin:NADP+ reductase system. Protein Sci 19:2073-84
Ctrnáctá, Vlasta; Fritzler, Jason M; Surinová, Mária et al. (2010) Efficacy of S-adenosylhomocysteine hydrolase inhibitors, D-eritadenine and (S)-DHPA, against the growth of Cryptosporidium parvum in vitro. Exp Parasitol 126:113-6
Rider Jr, Stanley Dean; Zhu, Guan (2010) Cryptosporidium: genomic and biochemical features. Exp Parasitol 124:2-9

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