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Reduced pathogenicity of a Candida albicans MAP kinase phosphatase (CPP1) mutant in the murine mastitis model
F A Guhad1, C Csank, H E Jensen
1Department of Physiology, Uppsala University, Sweden.
Abstract:
Candida albicans strains with a deletion of the mitogen-activated protein kinase tyrosine phosphatase gene (CPP1) are derepressed in the yeast-to-hyphal transition on solid surfaces in vitro at ambient temperatures and this gene is therefore required for repression of the yeast-to-hyphal switch. The pathology caused by a CPP1 null mutant strain was compared with that of the null mutant into which the wild-type CPP1 gene was introduced by homologous recombination and with the wild-type parent strain in a murine mycotic mastitis model. The mammary glands of lactating mice (at day 5 postpartum) were infected for 2, 4 and 6 days with 1 x 10(5), 1 x 10(6) and 1 x 10(7) cell-forming units before euthanasia. Infected and non-infected control glands were evaluated histopathologically. The null mutant strains showed less severe pathology than the two control strains. The Cpplp tyrosine phosphatase may thus be considered a virulence determinant during localized infection in C. albicans.
Insights
The CPP1 gene is essential for Candida albicans to switch to its hyphal form. Deleting this gene reduces the severity of infection in a mouse model, suggesting CPP1 is a virulence factor.
Area of Science:
- Medical Mycology
- Molecular Biology
- Pathogenesis
Background:
- Candida albicans undergoes a yeast-to-hyphal transition crucial for its pathogenesis.
- The mitogen-activated protein kinase tyrosine phosphatase gene (CPP1) regulates this morphological switch.
- Understanding CPP1's role is key to deciphering C. albicans virulence.
Purpose of the Study:
- To investigate the role of the CPP1 gene in the yeast-to-hyphal transition.
- To evaluate the impact of CPP1 deletion on C. albicans virulence in a murine model of mycotic mastitis.
Main Methods:
- Generating CPP1 null mutant strains of Candida albicans.
- Infecting lactating mice with wild-type and CPP1 null mutant strains.
- Histopathological evaluation of mammary glands to assess infection severity.
Main Results:
- CPP1 deletion strains showed derepression of the yeast-to-hyphal transition in vitro.
- CPP1 null mutant strains exhibited less severe pathology in the murine mastitis model compared to wild-type strains.
- The CPP1 gene is required for the repression of the yeast-to-hyphal switch.
Conclusions:
- The CPP1 gene is a critical regulator of the yeast-to-hyphal transition in Candida albicans.
- CPP1 functions as a virulence determinant in localized C. albicans infections.
- Targeting CPP1 may offer a strategy to reduce Candida albicans pathogenicity.
