National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI109025
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U24 GM139168
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM134020
United States
National Science Foundation (NSF, United States)
DBI-2238093
United States
Department of Energy (DOE, United States)
DE-SC0019313
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM147027
United States
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA)
R21DA056322
United States
Citation
Journal: Nat Commun / Year: 2025 Title: Molecular landscape of the fungal plasma membrane and implications for antifungal action. Authors: Jennifer Jiang / Mikhail V Keniya / Anusha Puri / Xueying Zhan / Jeff Cheng / Huan Wang / Gigi Lin / Yun-Kyung Lee / Nora Jaber / Caifeng Zhao / Cynthia Pang / Yasmine Hassoun / Haiyan Zheng ...Authors: Jennifer Jiang / Mikhail V Keniya / Anusha Puri / Xueying Zhan / Jeff Cheng / Huan Wang / Gigi Lin / Yun-Kyung Lee / Nora Jaber / Caifeng Zhao / Cynthia Pang / Yasmine Hassoun / Haiyan Zheng / Erika Shor / Zheng Shi / Sang-Hyuk Lee / Min Xu / David S Perlin / Wei Dai / Abstract: Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their native structure and spatial distribution remain poorly characterized. Herein, we employ an ...Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their native structure and spatial distribution remain poorly characterized. Herein, we employ an integrative approach to investigate the organization of plasma membrane protein complexes in Candida glabrata, focusing on two abundant and essential membrane proteins, the β-(1,3)-glucan synthase (GS) and the proton pump Pma1. We show that treatment with caspofungin, an echinocandin antifungal that targets GS, disrupts the native distribution of membrane protein complexes and alters membrane biophysical properties. Perturbation of the sphingolipid biosynthesis further modulates drug susceptibility, revealing that the lipid environment plays an integral role in membrane protein organization and GS-echinocandin interactions. Our work highlights the importance of characterizing membrane proteins in their native context to understand their functions and inform the development of novel antifungal therapies.
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