Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-17

AUTHORS

Yuya Ito, Taiga Miyazaki, Yutaka Tanaka, Takashi Suematsu, Hironobu Nakayama, Akihiro Morita, Tatsuro Hirayama, Masato Tashiro, Takahiro Takazono, Tomomi Saijo, Shintaro Shimamura, Kazuko Yamamoto, Yoshifumi Imamura, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae

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. More... »

PAGES

9789

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-66620-7

DOI

http://dx.doi.org/10.1038/s41598-020-66620-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1128524956

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32555245


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29 schema: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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37 Elm1
38 Galleria mellonella infection model
39 RNA sequencing
40 Saccharomyces
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43 agar plates
44 agents
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46 antifungal susceptibility
47 cell morphology
48 cell wall
49 cell wall components
50 cells
51 cellular functions
52 characterization
53 chitin content
54 components
55 content
56 cytokinesis
57 drug resistance
58 epithelial cells
59 expression levels
60 factors
61 first report
62 function
63 functional characterization
64 fungal pathogen Candida glabrata
65 fungi
66 genes
67 glabrata
68 growth
69 high temperature
70 important virulence factor
71 kinase
72 kinase activity
73 knowledge
74 levels
75 loss
76 model
77 morphogenesis
78 morphology
79 multiple cellular functions
80 pathogenic fungi
81 plate
82 report
83 resistance
84 response
85 role
86 sensitivity
87 sequencing
88 serine/threonine kinase
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