Turning on virulence: Mechanisms that underpin the morphologic transition and pathogenicity of Blastomyces

ABSTRACT

This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, Blastomyces dermatitidis, Blastomyces gilchristii, and Blastomyces percursus. In response to temperature, Blastomyces undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for Blastomyces and related thermally dimorphic fungi is essential for virulence. In the yeast phase, Blastomyces upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release. Blastomyces yeast also secrete dipeptidyl-peptidase IVA (DPPIVA), a serine protease that blunts the action of cytokines released from host immune cells. In vivo transcriptional profiling of Blastomyces yeast has uncovered genes such as PRA1 and ZRT1 involved in zinc scavenging that contribute to virulence during murine pulmonary infection. The discovery and characterization of genes important for virulence has led to advances at the bedside regarding novel diagnostics, vaccine development, and new targets for drug discovery.

KEYWORDS:

• Blastomyces
• Blastomycosis
• BAD1
• DRK1
• DPPIVA
• thermal dimorphism
• phase transition
• SREB

Acknowledgments

This work was supported by NIH grants R01 AI040996, R01 AI035681, R21 AI123758, U01 AI093553, and T32 AI055397 to BSK, and funds from the University of Wisconsin – Madison to GMG.

Additional information

Funding

National Institute of Allergy and Infectious Diseases, R01 AI040996, National Institute of Allergy and Infectious Diseases, R01 AI035681, National Institute of Allergy and Infectious Diseases, T32 AI055397, National Institute of Allergy and Infectious Diseases, U01 AI093553, National Institute of Allergy and Infectious Diseases, R21 AI123758.