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Updated: Dec 18, 2025
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
Yuya Ito1,2, Taiga Miyazaki3,4, Yutaka Tanaka5
1Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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.
Insights
The serine/threonine kinase Elm1 regulates cell morphology, stress response, and virulence in the pathogenic fungus Candida glabrata. Its kinase activity is crucial for these functions, impacting chitin content and adhesion.
Area of Science:
- Mycology
- Molecular Biology
- Pathogen Research
Background:
- Elm1 kinase is known for roles in Saccharomyces cerevisiae, including cytokinesis and morphogenesis.
- Its function in pathogenic fungi, particularly Candida glabrata, remains largely uncharacterized.
Purpose of the Study:
- To investigate the roles of Elm1 in cell morphology, stress response, and virulence in Candida glabrata.
- To determine if Elm1's kinase activity is essential for its functions in this pathogen.
Main Methods:
- Construction of ELM1-deletion, ELM1-reconstituted, ELM1-overexpression, and ELM1-kinase-dead strains in Candida glabrata.
- Analysis of cell morphology, cell wall composition (chitin content), growth under stress conditions (temperature, cell-wall damaging agents), and virulence in a Galleria mellonella model.
- RNA sequencing to assess gene expression changes, particularly for adhesion-related genes.
Main Results:
- The elm1Δ strain exhibited elongated morphology, increased chitin content, and a thicker cell wall.
- Loss of Elm1 led to increased sensitivity to heat and cell-wall damaging agents but enhanced virulence and adhesion to agar and epithelial cells.
- RNA sequencing revealed elevated expression of 30 adhesion-like genes in the elm1Δ strain.
- All observed phenotypes were dependent on Elm1's kinase activity.
Conclusions:
- Elm1 plays a significant role in regulating cell morphology, stress tolerance, adhesion, and virulence in the pathogenic fungus Candida glabrata.
- Elm1's kinase activity is essential for mediating these functions.
- This study provides the first functional characterization of Elm1 in pathogenic fungi.
