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Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata

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-overexpre...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299981/
https://www.ncbi.nlm.nih.gov/pubmed/32555245
http://dx.doi.org/10.1038/s41598-020-66620-7
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author 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
author_facet 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
author_sort Ito, Yuya
collection PubMed
description 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.
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spelling pubmed-72999812020-06-18 Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata 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 Sci Rep Article 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. Nature Publishing Group UK 2020-06-17 /pmc/articles/PMC7299981/ /pubmed/32555245 http://dx.doi.org/10.1038/s41598-020-66620-7 Text en © 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/.
spellingShingle Article
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
Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title_full Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title_fullStr Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title_full_unstemmed Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title_short Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
title_sort roles of elm1 in antifungal susceptibility and virulence in candida glabrata
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299981/
https://www.ncbi.nlm.nih.gov/pubmed/32555245
http://dx.doi.org/10.1038/s41598-020-66620-7
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