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Assay for Adhesion and Agar Invasion in S. cerevisiae
Published on: November 8, 2006
The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1-Pathway in Candida albicans
Elvira Román1, Rebeca Alonso-Monge1, Alberto Miranda1
1Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain.
Abstract:
The cell wall integrity pathway (CWI) plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the resultant mutants were characterised. We show here that Mkk2 mediates the phosphorylation of the Mkc1 MAPK in response to cell wall assembly interfering agents such as zymolyase or tunicamycin and also to oxidative stress. Remarkably, mkk2 and mkc1 mutants display related but distinguishable- cell wall associated phenotypes and differ in the pattern of MAPK phosphorylation under different stress conditions. mkk2 and mkc1 mutants display an altered expression of GSC1, CEK1 and CRH11 genes at different temperatures. Combined deletion of MKK2 with HST7 supports a cooperative role for the Cek1-mediated and CWI pathways in regulating cell wall architecture under vegetative growth. However, and in contrast to Mkc1, Mkk2 does not seem to play a role in the virulence of C. albicans in the mouse systemic model or the Galleria mellonella model of infection.
Insights
The MKK2 gene deletion in Candida albicans impacts cell wall integrity by altering MAPK phosphorylation and gene expression. However, Mkk2 does not influence fungal virulence in infection models.
Area of Science:
- Mycology
- Molecular Biology
- Cell Biology
Background:
- The cell wall integrity pathway (CWI) is crucial for fungal cell wall biogenesis.
- Candida albicans is an opportunistic fungal pathogen where CWI is essential.
Purpose of the Study:
- To investigate the role of the MKK2 gene, encoding a MAPKK in the CWI pathway, in Candida albicans.
- To characterize the phenotypes of MKK2 deletion mutants and their response to stress.
Main Methods:
- Gene deletion of MKK2 in different Candida albicans backgrounds.
- Phenotypic characterization of resultant mutants.
- Analysis of MAPK phosphorylation patterns and gene expression under various stress conditions.
Main Results:
- Mkk2 mediates Mkc1 MAPK phosphorylation in response to cell wall stress (zymolyase, tunicamycin) and oxidative stress.
- mkk2 and mkc1 mutants exhibit distinct cell wall phenotypes and differential MAPK phosphorylation patterns.
- Altered expression of GSC1, CEK1, and CRH11 genes observed in mkk2 and mkc1 mutants at different temperatures.
- Combined deletion of MKK2 and HST7 suggests a cooperative role in cell wall architecture.
Conclusions:
- Mkk2 is a key component of the CWI pathway in Candida albicans, regulating Mkc1 phosphorylation and gene expression.
- While Mkk2 influences cell wall integrity, it does not appear to play a significant role in Candida albicans virulence.
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