Comparison of / Species Complex to Related Genera ( and ) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility.

Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus includes several species distributed around the world. The / species complex is largely responsible for most cases of cryptococcosis. However, clinical series have been published of infections caused by () and (), among other related genera. Here, we examined the pathogenic potential and antifungal susceptibility of / species complex (clades I and II) and related genera ( and ) isolated from environmental and clinical samples. . (clade III), . (clade IV) and /. (clade V) strains produced higher levels of phospholipase and hemolysins, whereas the / species complex strains (clades I and II) had markedly thicker capsules, produced more biofilm biomass and melanin, which are known virulence attributes. Interestingly, 40% of . strains (clade II) had MICs above the ECV established for this species to amphotericin B. Several non-/ species complex (clades III to V) had MICs equal to or above the ECVs established for and for all the three antifungal drugs tested. Finally, all the non- clinical isolates (clades III to V) produced more melanin than the environmental isolates might reflect their particularly enhanced need for melanin during protection. It is very clear that / species complex (clades I and II) strains, in general, show more similar virulence phenotypes between each other when compared to non-/ species complex (clades III to V) isolates. These observations together with the fact that . and spp. (clades III to V) strains were collected from the outside of a University Hospital, identify features of these yeasts important for environmental and patient colonization and furthermore, define mechanisms for infections with these uncommon pathogens.