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Candida albicans RIM101 pH response pathway is required for host-pathogen interactions
D Davis1, J E Edwards, A P Mitchell
1Department of Microbiology, Columbia University, New York, New York 10032, USA. dd251@columbia.edu
Infection and Immunity
|September 19, 2000
Summary
The RIM101 pathway is essential for Candida albicans virulence in mice. This pathway, including Rim8p, is crucial for fungal pathogenesis and damaging host cells during systemic candidiasis.
Area of Science:
- Mycology
- Pathogenesis
- Molecular Biology
Background:
- Candida albicans environmental adaptability is key to its pathogenicity.
- The RIM101 pathway regulates gene expression and morphology in response to pH.
- Its role in vivo pathogenesis remains to be fully elucidated.
Purpose of the Study:
- To determine the in vivo necessity of the RIM101 pathway for C. albicans pathogenesis.
- To investigate the function of Rim8p in the context of the RIM101 pathway during infection.
Main Methods:
- Utilized mouse model of hematogenously disseminated systemic candidiasis.
- Assessed virulence, kidney pathology, and endothelial cell damage in C. albicans mutants.
- Employed an activated allele (RIM101-405) to study pathway rescue.
Main Results:
- rim101(-) and rim8(-) mutants exhibited significantly reduced virulence and kidney pathology.
- These mutants displayed impaired endothelial cell damage in situ.
- RIM101-405 suppressed rim8(-) defects, rescuing virulence and pathogenicity markers in vivo.
Conclusions:
- The RIM101 pathway is indispensable for C. albicans virulence in a systemic infection model.
- Rim8p functions upstream to activate Rim101p, which is critical for pathogenesis.
- This pathway represents a potential target for antifungal therapies.
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