Increased virulence and competitive advantage of a/α over a/a or α/α offspring conserves the mating system of Candida albicans

The majority of Candida albicans strains in nature are a/alpha and Must undergo homozygosis to a/a or ala to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/a strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/a strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/a and offspring a/a or alpha/alpha cells were co-injected, a/a always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha 2 strain and its isogenic a/a parent strain were coinjected, the a/a/a2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/a genotype that conserves the mating system of C. albicans in nature.