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Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata

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Title: Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
Authors: Ito, Yuya / Miyazaki, Taiga / Tanaka, Yutaka / Suematsu, Takashi / Nakayama, Hironobu / Morita, Akihiro / Hirayama, Tatsuro / Tashiro, Masato / Takazono, Takahiro / Saijo, Tomomi / Shimamura, Shintaro / Yamamoto, Kazuko / Imamura, Yoshifumi / Izumikawa, Koichi / Yanagihara, Katsunori / Kohno, Shigeru / Mukae, Hiroshi
Issue Date: 17-Jun-2020
Publisher: Springer Nature
Citation: Scientific Reports, 10(1), art.no.9789; 2020
Abstract: Elm1 is a serine/threonine kinase involved in multiple cellular functions, including cytokinesis, morphogenesis, and drug resistance in Saccharomyces cerevisiae; however, its roles in pathogenic fungi have not been reported. In this study, we created ELM1-deletion, ELM1-reconstituted, ELM1-overexpression, and ELM1-kinase-dead strains in the clinically important fungal pathogen Candida glabrata and investigated the roles of Elm1 in cell morphology, stress response, and virulence. The elm1Δ strain showed elongated morphology and a thicker cell wall, with analyses of cell-wall components revealing that this strain exhibited significantly increased chitin content relative to that in the wild-type and ELM1-overexpression strains. Although the elm1Δ strain exhibited slower growth than the other two strains, as well as increased sensitivity to high temperature and cell-wall-damaging agents, it showed increased virulence in a Galleria mellonella-infection model. Moreover, loss of Elm1 resulted in increased adhesion to agar plates and epithelial cells, which represent important virulence factors in C. glabrata. Furthermore, RNA sequencing revealed that expression levels of 30 adhesion-like genes were elevated in the elm1Δ strain. Importantly, all these functions were mediated by the kinase activity of Elm1. To our knowledge, this is the first report describing the functional characterization of Elm1 in pathogenic fungi.
URI: http://hdl.handle.net/10069/40098
DOI: 10.1038/s41598-020-66620-7
Rights: © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/40098

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