Associations of genetic variation and clinical characteristics of Blastomyces dermatitidis infections in Wisconsin

Abstract

Blastomyces dermatitidis is a thermally dimorphic fungus which exists as a mold in the environment. Upon inhalation of infectious spores by a susceptible mammalian host, the mold converts into a pathogenic yeast. The organism causes the disease blastomycosis, which often presents as an acute pulmonary infection but can progress to chronic pulmonary disease with dissemination to other organs. Because tremendous variation is seen in the clinical presentation of this disease, we hypothesized that genetic diversity within this organism was associated with differences in clinical presentation and outcome. To test this hypothesis, 27 microsatellite markers were developed to analyze the population genetic structure of 238 B. dermatitidis human clinical isolates from Wisconsin. Structure and principal component analyses identified two distinct populations, one highly clonal (Group 1; n=135) and the other polymorphic (Group 2; n=103). Using unconditional logistic regression modeling, we identified significant differences between clinical characteristics of blastomycosis disease between these two groups. Patients infected with Group 2 isolates reported more skin lesions (p=<0.0001) and were more likely to be immunocompromised (p=0.0001), whereas infections caused by Group 1 isolates were more often associated with pulmonary involvement including chest pain (p=0.0165), cough (p=0.0156), fever (p=<0.0001), and hospitalization (p=0.0417). This study supports the hypothesis that associations of clinical presentation and disease outcome to organism genotype exists. Further research is required to determine the genetic factors that explain the differences in clinical presentation and outcome.