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Published on: October 18, 2017
Reduced virulence of Candida albicans PHR1 mutants
M A Ghannoum1, B Spellberg, S M Saporito-Irwin
1Division of Infectious Diseases, Harbor-UCLA Research and Education Institute, St. John's Cardiovascular Research Center, Torrance 90509, USA.
Abstract:
Candida albicans mutants lacking PHR1 exhibit a pH-dependent morphogenic defect which is expressed at pH 7.5, a pH comparable to that of mammalian blood (S. M. Saporito-Irwin, C. E. Birse, P. S. Sypherd, and W. A. Fonzi, Mol. Cell. Biol. 15:601-613, 1995). The in vivo relevance of this expression pattern was tested in a mouse model of systemic candidiasis. A phr1/phr1 mutant was found to be less virulent than an isogenic Phr1+ strain and exhibited altered morphological development in vivo. These results indicate that PHR1 contributes to the virulence of C. albicans.
Insights
Candida albicans mutants lacking PHR1 show a pH-dependent defect. This PHR1 gene is crucial for virulence in systemic candidiasis, as shown in a mouse model.
Area of Science:
- Medical Mycology
- Molecular Biology
- Infectious Diseases
Background:
- Candida albicans is an opportunistic fungal pathogen.
- The PHR1 gene in C. albicans is involved in morphogenic transitions.
- Morphogenesis in C. albicans is often pH-dependent, particularly at physiological pH.
Purpose of the Study:
- To investigate the in vivo relevance of the pH-dependent morphogenic defect in C. albicans mutants lacking PHR1.
- To determine the role of PHR1 in the virulence of C. albicans during systemic infection.
- To assess the morphological development of phr1/phr1 mutants in a mammalian host.
Main Methods:
- Generation of Candida albicans mutants lacking the PHR1 gene (phr1/phr1).
- Infection of a mouse model to study systemic candidiasis.
- Comparison of virulence between isogenic Phr1+ and phr1/phr1 strains.
- Analysis of in vivo morphological development of the mutant strain.
Main Results:
- Candida albicans mutants lacking PHR1 exhibited a pH-dependent morphogenic defect at pH 7.5.
- The phr1/phr1 mutant demonstrated reduced virulence compared to the isogenic Phr1+ strain in the mouse model.
- Altered morphological development of the phr1/phr1 mutant was observed in vivo.
Conclusions:
- The PHR1 gene plays a significant role in the virulence of Candida albicans.
- PHR1 is essential for proper in vivo morphological adaptation and pathogenicity.
- Targeting PHR1 could be a potential strategy for treating systemic candidiasis.
