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Molecular basis of pathogenicity in Blastomyces dermatitidis: the importance of adhesion
1Department of Pediatrics and the Comprehensive Cancer Center, University of Wisconsin Medical School, Madison, USA. bsklein@facstaff.wisc.edu
Abstract:
An understanding of the molecular bases of pathogenicity in Blastomyces dermatitidis and related systemic dimorphic fungi has been limited until recent years. Yeast cells of B. dermatitidis display an adhesion promoting protein termed WI-1. Recent studies entailing homologous gene targeting and mutation of WI-1 have provided null mutants at this locus and demonstrated the crucial role of the WI-1 adhesin in pathogenesis of blastomycosis. Ongoing studies are pointing to a link between phase-specific expression of WI-1 and the observation that transition to yeast cells is essential for the acquisition of pathogenicity by B. dermatitidis. Recombinant attenuated yeast that lack WI-1 are serving as invaluable tools for induction of vaccine resistance and are pointing to new insights about adaptive immunity to B. dermatitidis.
Insights
The WI-1 adhesin is crucial for Blastomyces dermatitidis pathogenicity. Gene mutation studies reveal WI-1
Area of Science:
- Medical Mycology
- Molecular Pathogenesis
- Immunology
Background:
- Limited understanding of molecular mechanisms underlying pathogenicity in Blastomyces dermatitidis and related systemic dimorphic fungi.
- Blastomyces dermatitidis yeast cells express an adhesion-promoting protein called WI-1.
- Recent advancements have begun to elucidate the role of specific fungal molecules in disease development.
Purpose of the Study:
- To investigate the role of the WI-1 adhesin in the pathogenesis of blastomycosis.
- To explore the relationship between phase-specific expression of WI-1 and fungal pathogenicity.
- To utilize WI-1 deficient mutants for vaccine development and understanding adaptive immunity.
Main Methods:
- Homologous gene targeting and mutation of the WI-1 gene in Blastomyces dermatitidis.
- Generation of WI-1 null mutants.
- Development of recombinant attenuated yeast vaccines lacking WI-1.
Main Results:
- Mutation of WI-1 demonstrated its crucial role in the pathogenesis of blastomycosis.
- Evidence suggests a link between phase-specific expression of WI-1 and acquisition of pathogenicity during yeast-phase transition.
- WI-1 deficient attenuated yeast strains are effective in inducing vaccine resistance.
Conclusions:
- The WI-1 adhesin is a key virulence factor in Blastomyces dermatitidis.
- Phase-specific expression of WI-1 is essential for fungal pathogenicity.
- WI-1 deficient yeast offer a promising platform for developing vaccines against blastomycosis and studying host immune responses.