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PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis
S M Saporito-Irwin1, C E Birse, P S Sypherd
1Department of Microbiology and Molecular Genetics, California College of Medicine, University of California, Irvine 92717.
Abstract:
Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an opportunistic pathogen of humans. Morphogenesis and alterations in cell shape require integration of many cellular functions and occur in response to environmental signals, most notably pH and temperature in the case of C. albicans. In the course of our studies of differential gene expression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of the culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein attached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditional morphological defect. At alkaline pH, the mutant, unlike the parental type, was unable to conduct apical growth of either yeast or hyphal growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.
Insights
The gene PHR1 in Candida albicans is crucial for cell shape changes. Its absence causes defects in apical growth at alkaline pH, impacting this opportunistic pathogen's morphogenesis.
Area of Science:
- Mycology
- Cell Biology
- Medical Mycology
Background:
- Candida albicans, an opportunistic human pathogen, displays morphological plasticity influenced by environmental factors like pH.
- This plasticity is vital for its pathogenic capabilities and requires coordinated cellular functions.
Purpose of the Study:
- To investigate the role of a novel pH-regulated gene, PHR1, in Candida albicans morphogenesis.
- To understand the function of PHR1 in cellular shape determination and growth.
Main Methods:
- Differential gene expression analysis to identify pH-regulated genes.
- Construction and characterization of a homozygous null mutant for the PHR1 gene.
- Microscopic analysis of cell morphology and growth under varying pH conditions.
Main Results:
- PHR1 expression is induced at alkaline pH (above 5.5) and repressed at acidic pH.
- A PHR1 null mutant exhibits a pH-conditional defect in apical growth for both yeast and hyphal forms at alkaline pH.
- The morphological defect in the mutant was not linked to impaired cytoskeletal polarization or secretion.
Conclusions:
- PHR1 plays a critical role in regulating apical cell growth and morphogenesis in Candida albicans.
- The PHR1 gene product likely represents a novel component essential for fungal development and pathogenicity.
- Understanding PHR1 function provides insights into the mechanisms of fungal dimorphism and host-pathogen interactions.