Identification of the Mating-Type (MAT) Locus That Controls Sexual Reproduction of Blastomyces dermatitidis

Abstract

c Blastomyces dermatitidis is a dimorphic fungal pathogen that primarily causes blastomycosis in the midwestern and northern United States and Canada. While the genes controlling sexual development have been known for a long time, the genes controlling sexual reproduction of B. dermatitidis (teleomorph, Ajellomyces dermatitidis) are unknown. We identified the mating-type (MAT) locus in the B. dermatitidis genome by comparative genomic approaches. The B. dermatitidis MAT locus resembles those of other dimorphic fungi, containing either an alpha-box (MAT1-1) or an HMG domain (MAT1-2) gene linked to the APN2, SLA2, and COX13 genes. However, in some strains of B. dermatitidis, the MAT locus harbors transposable elements (TEs) that make it unusually large compared to the MAT locus of other dimorphic fungi. Based on the MAT locus sequences of B. dermatitidis, we designed specific primers for PCR determination of the mating type. Two B. dermatitidis isolates of opposite mating types were cocultured on mating medium. Immature sexual structures were observed starting at 3 weeks of coculture, with coiled-hyphae-containing cleistothecia developing over the next 3 to 6 weeks. Genetic recombination was detected in potential progeny by mating-type determination, PCR-restriction fragment length polymorphism (PCR-RFLP), and random amplification of polymorphic DNA (RAPD) analyses, suggesting that a meiotic sexual cycle might have been completed. The F1 progeny were sexually fertile when tested with strains of the opposite mating type. Our studies provide a model for the evolution of the MAT locus in the dimorphic and closely related fungi and open the door to classic genetic analysis and studies on the possible roles of mating and mating type in infection and virulence.

Discovery of a Sexual Cycle in Aspergillus lentulus, a Close Relative of A. fumigatus

“…A MAT1-2-4 gene has also been reported for Coccidioides immitis and C. posadasii (51, 52), but this shares little sequence conservation with the MAT1-2-4 proteins from the aspergilli and is absent from the MAT loci of many other heterothallic eurotiomycete species, such as those recently described for Blastomyces dermatitidis (53). …”

The cryptic sexual strategies of human fungal pathogens

“…Recently, a MAT locus was identified in the ascomycete Blastomyces dermatitidis 151 . This dimorphic fungal pathogen is the leading cause of blastomycosis, causing severe respiratory and disseminated disease in immunocompetent humans.…”

“…Distribution of mating types and population genetics studies suggest that B. dermatitidis might reproduce sexually, but the mating-type locus had not been described 152,153 . The identification of the B. dermatitidis MAT revealed that, unlike the MAT loci of other dimorphic fungi, it contains transposable elements (TEs) that make it unusually large and may increase sequence diversity between the two MAT idiomorphs while decreasing recombination within this region 151 . It remains unclear, however, if this fungus undergoes sexual reproduction in nature and, if so, whether the resulting sexual spores are infectious.…”

Clinical and molecular epidemiology of veterinary blastomycosis in Wisconsin

“…Very little work has been done exploring genetic recombination in B. dermatitidis . Although B. dermatitidis can reproduce sexually, the mating-type locus was only recently identified [25], and it is unknown how frequently sexual reproduction occurs in nature. The rate of recombination between and among the 2 major genetic groups of B. dermatitidis could significantly impact the population genetic structure of this pathogen.…”