Molecular landscape of the fungal plasma membrane and implications for antifungal action
Jiang, Jennifer Keniya, Mikhail V. Puri, Anusha Zhan, Xueying Cheng, Jeff Wang, Huan Lin, Gigi Lee, Yun-Kyung Jaber, Nora Zhao, Caifeng
Jiang, Jennifer
Keniya, Mikhail V.
Puri, Anusha
Zhan, Xueying
Cheng, Jeff
Wang, Huan
Lin, Gigi
Lee, Yun-Kyung
Jaber, Nora
Zhao, Caifeng
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Computer Vision
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Journal article
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2025
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English
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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 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.
Citation
J. Jiang et al., “Molecular landscape of the fungal plasma membrane and implications for antifungal action,” Nat Commun, vol. 16, no. 1, p. 9125, Dec. 2025, doi: 10.1038/S41467-025-64171-X
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Nature Communications
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Springer Nature