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Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata.
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.
Afiliación
  • Minematsu A; Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Miyazaki T; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Shimamura S; Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Nishikawa H; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Nakayama H; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Takazono T; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Saijo T; Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, Mie, Japan.
  • Yamamoto K; Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Imamura Y; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Yanagihara K; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Kohno S; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Mukae H; Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
  • Izumikawa K; Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
PLoS One ; 14(1): e0210883, 2019.
Article en En | MEDLINE | ID: mdl-30673768
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virulencia / Proteínas Fúngicas / ATPasas de Translocación de Protón Vacuolares / Farmacorresistencia Fúngica / Farmacorresistencia Fúngica Múltiple / Candida glabrata Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virulencia / Proteínas Fúngicas / ATPasas de Translocación de Protón Vacuolares / Farmacorresistencia Fúngica / Farmacorresistencia Fúngica Múltiple / Candida glabrata Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos