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A lipid metabolic map of the pathogenic fungus Histoplasma capsulatum

biorxiv. 2020; 
Daniel Zamith-Miranda,  Heino M. Heyman,  Meagan C. Burnet,  Sneha P. Couvillion,  Xueyun Zheng,  Nathalie Munoz,  Jennifer E. Kyle,  Erika M. Zink,  Karl K. Weitz,  Kent J. Bloodsworth,  Geremy Clair, Jeremy D. Zucker,  Jeremy R. Teuton, Samuel H. Payne,  Young-Mo Kim,  Morayma Reyes Gil,  Erin S. Baker,  Erin L. Bredeweg,  Joshua D. Nosanchuk, Ernesto S. Nakayasu
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摘要

Lipids play a fundamental role in fungal cell biology, being components of the cell membrane as well as targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by integrating proteomic and lipidomic analyses. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We also found that H. capsulatumproduces analogs of platelet-activating factor, a potent regulator of the human immune response. The H. capsulatum platelet-activating factor ana... More

关键词

Histoplasma capsulatum, lipid metabolism, drug target, platelet-activating factor, multi-omics analysis