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Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata

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タイトル: Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata
著者: Minematsu, Asuka / Miyazaki, Taiga / Shimamura, Shintaro / Nishikawa, Hiroshi / Nakayama, Hironobu / Takazono, Takahiro / Saijo, Tomomi / Yamamoto, Kazuko / Imamura, Yoshifumi / Yanagihara, Katsunori / Kohno, Shigeru / Mukae, Hiroshi / Izumikawa, Koichi
発行日: 2019年 1月23日
出版者: Public Library of Science
引用: PLoS ONE, 14(1), art.no.e0210883; 2019
抄録: Vacuolar proton-translocating ATPase (V-ATPase) is located in fungal vacuolar membranes.It is involved in multiple cellular processes, including the maintenance of intracellular ion homeostasis by maintaining acidic pH within the cell. The importance of V-ATPase in virulence has been demonstrated in several pathogenic fungi, including Candida albicans. However, it remains to be determined in the clinically important fungal pathogen Candida glabrata.Increasing multidrug resistance of C. glabrata is becoming a critical issue in the clinical setting. In the current study, we demonstrated that the plecomacrolide V-ATPase inhibitor bafilomycin B1 exerts a synergistic effect with azole antifungal agents, including fluconazole and voriconazole, against a C. glabrata wild-type strain. Furthermore,the deletion of the VPH2 gene encoding an assembly factor of V-ATPase was sufficient to interfere with V-ATPase function in C. glabrata, resulting in impaired pH homeostasis in the vacuole and increased sensitivity to a variety of environmental stresses, such as alkaline conditions (pH 7.4), ion stress (Na+, Ca2+, Mn2+, and Zn2+ stress),exposure to the calcineurin inhibitor FK506 and antifungal agents (azoles and amphotericin B), and iron limitation. In addition, virulence of C. glabrata Δvph2 mutant in a mouse model of disseminated candidiasis was reduced in comparison with that of the wild-type and VPH2-reconstituted strains.These findings support the notion that V-ATPase is a potential attractive target for the development of effective antifungal strategies.
URI: http://hdl.handle.net/10069/38805
DOI: 10.1371/journal.pone.0210883
権利: ©2019 Minematsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38805



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