The PI and her collaborators propose to continue their studies on the biochemical characterization of the lipids of Pneumocystis carinii (Pc). The long term goal of this project is to better understand the lipid biochemistry of this pathogen. To further the lipid studies, the PI has presented four specific aims in this current proposal.
The first aim i s: To examine the pathway and mechanisms by which cis-9,10-epoxy stearic acid (signature lipid) is synthesized by Pc, and to characterize the lipoxygenase (lipoxidase) enzyme activity.
The second aim i s: to analyze lipid modifications of purified major surface glycoprotein preparations isolated from Pc, identify the lipidated sites on the molecules, and examine whether these molecules contain inositol-lipid anchors.
The third aim of the proposal is: To identify and characterize Pc sphingolipids in detail, to examine their biosynthesis, and to determine whether the organism releases long-chain bases, ceramides and/or fumonisns or fumonism-like sphingoid bases. Finally, the fourth aim is: To characterize the lipids of human-derived P.c. hominis focusing on Pc specific """"""""signature"""""""" molecules.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS and Related Research Study Section 5 (ARRE)
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Dixon (Dmid), Dennis M
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University of Cincinnati
Schools of Arts and Sciences
United States
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Wyder, Michael A; Johnston, Laura Q; Kaneshiro, Edna S (2010) Evidence for DNA synthesis in Pneumocystis carinii trophozoites treated with the beta-1,3-glucan synthesis inhibitor pneumocandin L-693,989. J Eukaryot Microbiol 57:447-8
Basselin, Mireille; Hunt, Shannon M; Abdala-Valencia, Hiam et al. (2005) Ubiquinone synthesis in mitochondrial and microsomal subcellular fractions of Pneumocystis spp.: differential sensitivities to atovaquone. Eukaryot Cell 4:1483-92
Giner, Jose-Luis; Zhao, Hui; Amit, Zunika et al. (2004) Sterol composition of Pneumocystis jirovecii with blocked 14alpha-demethylase activity. J Eukaryot Microbiol 51:634-43
Kaneshiro, Edna S (2004) Sterol metabolism in the opportunistic pathogen Pneumocystis: advances and new insights. Lipids 39:753-61
Kaneshiro, Edna S; Basselin, Mireille; Hunt, Shannon M (2003) Evidence that biosynthesis of individual ubiquinone homologs in Pneumocystis carinii is under homolog-specific negative feedback (product) control. J Eukaryot Microbiol 50 Suppl:622-3
Zhao, Hui; Giner, Jose-Luis; Kaneshiro, Edna S (2003) Definitive structural identities of Pneumocystis jirovecii sterols. J Eukaryot Microbiol 50 Suppl:680
Worsham, D Nicole; Basselin, Mireille; Smulian, A George et al. (2003) Evidence for cholesterol scavenging by Pneumocystis and potential modifications of host-synthesized sterols by the P. carinii SAM:SMT. J Eukaryot Microbiol 50 Suppl:678-9
Giner, Jose-Luis; Zhao, Hui; Beach, David H et al. (2002) Comprehensive and definitive structural identities of Pneumocystis carinii sterols. J Lipid Res 43:1114-24
Kaneshiro, Edna S; Rosenfeld, Jill A; Basselin-Eiweida, Mireille et al. (2002) The Pneumocystis carinii drug target S-adenosyl-L-methionine:sterol C-24 methyl transferase has a unique substrate preference. Mol Microbiol 44:989-99
Kaneshiro, Edna S (2002) Is Pneumocystis a plant? J Eukaryot Microbiol 49:367-73

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