Phenotypic switching and mating type switching of Candida glabrata at sites of colonization

Candida glabrata switches spontaneously at high frequency among the following four graded phenotypes discriminated on agar containing 1 mM CuSO4: white, light brown, dark brown (DB), and very dark brown. C. glabrata also contains three mating type loci with a configuration similar to that of the Saccharomyces cerevisiae mating type cassette system, suggesting it may also undergo cassette switching at the expression locus MTL1. To analyze both reversible, high-frequency phenotypic switching and mating type switching at sites of colonization, primary samples from the oral cavities and vaginal canals of three patients suffering from C. glabrata vaginitis were clonally plated on agar containing CuSO4. It was demonstrated that (i) in each vaginitis patient, there was only one colonizing strain; (ii) an individual could have vaginal colonization without oral colonization; (iii) phenotypic switching occurred at sites of colonization; (iv) the DB phenotype predominated at the site of infection in all three patients; (v) genetically unrelated strains switched in similar, but not identical, fashions and caused vaginal infection; (vi) different switch phenotypes of the same strain could simultaneously dominate different body locations in the same host; (vii) pathogenesis could be caused by cells in different mating type classes; and (viii) mating type switching demonstrated at both the genetic and transcription levels occurred in one host.