2009 Fiscal Year Final Research Report
Functional analysis of a novel member of heat shock 70 protein in quorum sensing system of pathogenic fungus Candida albicans
| Project/Area Number |
20890274
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| Research Category |
Grant-in-Aid for Young Scientists (Start-up)
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| Allocation Type | Single-year Grants |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
NAGAO Jun-ichi Fukuoka Dental College, 歯学部, 助教 (30509047)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 病原性真菌 / 形態変換 / シグナル伝達 / Heat shock protein |
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| Research Abstract |
MSI3 (multicopy suppressor of ira1 mutant, which causes hyperactivation of the Ras-cAMP-PKA pathway) was isolated as a gene involved in early yeast-hyphal transition of Candida albicans and is a novel member of the heat shock protein 70 family. Previously, we showed that MSI3 expression is quickly and significantly downregulated in N-acetyl-D-glucosamine (GlcNAc)-induced germination. We generated a mutant strain, tetMSI3, in which MSI3 is controlled under the tetracycline-regulatable promoter and we compared various phenotypes with those of the parent strain CAF2. Negative regulation of MSI3 expression with the tetracycline analog doxycycline resulted in a growth defect in tetMSI3 cells. In the absence of doxycycline, MSI3 expression was approximately 4-fold higher in tetMSI3 cells than in CAF2 cells in a growth medium, which increased the susceptibility to cell wall inhibitors. MSI3 expression was drastically reduced in response to GlcNAc in CAF2 cells. The results suggested that a drastic reduction in MSI3 expression by GlcNAc activates the Ras1-cAMP-PKA pathway, thus stimulating germination and also inducing resistance to hydrogen peroxide. Reduced expression and overexpression of MSI3 resulted in avirulence and attenuated virulence, respectively, in a murine model. Our findings suggest that C. albicans Msi3p has multiple functions in cell growth, cell wall integrity, negative regulation of hyphal morphogenesis via the Ras1-cAMP-PKA pathway, susceptibility to hydrogen peroxide, and virulence.
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