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Altered expression of surface alpha-1,3-glucan in genetically related strains of Blastomyces dermatitidis that differ
1Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison 53792.
Abstract:
Recent studies of the dimorphic fungal pathogens Histoplasma capsulatum and Paracoccidioides brasiliensis have suggested a role in virulence for the cell surface carbohydrate alpha-(1,3)-glucan. To investigate a possible basis for alpha-(1,3)-glucan in the pathogenicity and virulence of the dimorphic fungus Blastomyces dermatitidis, we examined three genetically related strains of B. dermatitidis that differ in their virulence for mice: wild-type virulent strain ATCC 26199; mutant strain ATCC 60915, which is 10,000-fold reduced in virulence; and mutant strain ATCC 60916, which is avirulent. Immunologic quantitation of cell wall alpha-(1,3)-glucan revealed that the mutant yeasts were almost devoid of this sugar moiety, in contrast to the high concentration of alpha-(1,3)-glucan on the cell wall of the wild-type yeasts. These differences are discussed in relation to previous studies of yeast surface expression of the WI-1 antigen and recognition and binding of the related strains by human monocyte-derived macrophages.
Insights
Alpha-(1,3)-glucan on the cell surface of Blastomyces dermatitidis is crucial for virulence. Mutant strains lacking this carbohydrate showed significantly reduced pathogenicity in mouse models, indicating its importance in fungal infections.
Area of Science:
- Medical Mycology
- Pathogen Biology
- Carbohydrate Chemistry
Background:
- Dimorphic fungal pathogens like Histoplasma capsulatum and Paracoccidioides brasiliensis have cell surface alpha-(1,3)-glucan implicated in virulence.
- Blastomyces dermatitidis is a significant fungal pathogen requiring further understanding of its virulence factors.
Purpose of the Study:
- To investigate the role of alpha-(1,3)-glucan in the pathogenicity and virulence of Blastomyces dermatitidis.
- To correlate alpha-(1,3)-glucan expression with the virulence of different B. dermatitidis strains in a mouse model.
Main Methods:
- Examined three genetically related strains of B. dermatitidis with varying virulence (wild-type virulent, moderately virulent mutant, avirulent mutant).
- Quantified cell wall alpha-(1,3)-glucan levels using immunologic methods.
- Compared alpha-(1,3)-glucan concentration with observed virulence in mice.
Main Results:
- Wild-type virulent B. dermatitidis strains exhibited high concentrations of cell wall alpha-(1,3)-glucan.
- Mutant B. dermatitidis strains with reduced or no virulence were nearly devoid of alpha-(1,3)-glucan.
- A strong correlation was observed between alpha-(1,3)-glucan presence and fungal virulence.
Conclusions:
- Alpha-(1,3)-glucan is a critical virulence factor for Blastomyces dermatitidis.
- The absence of alpha-(1,3)-glucan significantly attenuates the pathogenicity of B. dermatitidis.
- Findings support the role of alpha-(1,3)-glucan in fungal-host interactions and suggest it as a potential therapeutic target.