Association between fertility and molecular sub-type of global isolates of Cryptococcus gattii molecular type VGII

The basidiomycetous yeast Cryptococcus gattii, is a primary pathogen which causes disease in apparently healthy humans and a wide range of animals. Recently, an outbreak of cryptococcosis caused by a previously uncommon genotype of C. gattii, VGII, emerged on Vancouver Island, British Columbia, Canada. Two pathogenic sub-types of VGII (designated VGIIa and VGIIb) were identified among these isolates. All of the isolates proved to be mating type alpha and had exceptionally high sporulation capacity. The common subtype, VGIIa, was more virulent than VGIIb in mice, suggesting a linkage between subtype and fertility/virulence. To test this hypothesis, we compared the fertility of 91 isolates from the Vancouver Island outbreak with that of 72 VGII isolates selected globally. Of all isolates, 69.94% were found to be fertile and exhibited clamp connections and basidiospores. The Vancouver isolates showed a high fertility rate of 84.2% as compared to only 29% of the 21 Australian isolates investigated. Mating type alpha strains were more fertile (72.79%) than mating type a (43.75%) (p<0.022). Amongst the two subtypes of VGII a much higher proportion of VGIIa (91.7%) than VGIIb (33.3%) was fertile (p<0.001). These results suggest that there is a clear correlation between the VGII subtypes of C. gattii and their mating/fertility. Further in vitro and in vivo investigations of more strains and congenic pairs are warranted.