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Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus  Cryptococcus  includes several species distributed around the world. The  C. gattii / neoformans  species complex is largely responsible for most cases of cryptococcosis. However, clinical series have been published of infections caused by  Papiliotrema  ( Cryptococcus )  laurentii  and  Naganishia albida  ( Cryptococcus albidus ), among other related genera. Here, we examined the pathogenic potential and antifungal susceptibility of  C. gattii / neoformans  species complex (clades I and II) and related genera ( Papiliotrema  and  Naganishia ) isolated from environmental and clinical samples.  P .  laurentii  (clade III),  N .  liquefasciens/N. albidosimilis  (clade IV) ;  and  N. adeliensis / N .  albida  (clade V) strains produced higher levels of phospholipase and hemolysins, whereas the  C. gattii / neoformans  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  C .  neoformans  strains (clade II) had MICs above the ECV established for this species to amphotericin B. Several non- C. gattii / neoformans  species complex (clades III to V) had MICs equal to or above the ECVs established for  C. deuterogattii  and  C. neoformans  for all the three antifungal drugs tested. Finally, all the non- C. gattii/neoformans  clinical isolates (clades III to V) produced more melanin than the environmental isolates might reflect their particularly enhanced need for melanin during  in vivo  protection. It is very clear that  C. gattii / neoformans  species complex (clades I and II) strains, in general, show more similar virulence phenotypes between each other when compared to non- C. gattii / neoformans  species complex (clades III to V) isolates. These observations together with the fact that  P .  laurentii  and  Naganishia  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.

frontiers in cellular and infection microbiology

Comparison of Cryptococcus gattii/neoformans Species Complex to Related Genera (Papiliotrema and Naganishia) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility