AUTHOR=Oliveira Lana Sarita de Souza , Pinto Luciana Magalhães , de Medeiros Mariana Araújo Paulo , Toffaletti Dena L. , Tenor Jennifer L. , Barros Tânia Fraga , Neves Rejane Pereira , Neto Reginaldo Gonçalves de Lima , Milan Eveline Pipolo , Padovan Ana Carolina Barbosa , Rocha Walicyranison Plinio da Silva , Perfect John R. , Chaves Guilherme Maranhão 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.642658

DOI=10.3389/fcimb.2021.642658

ISSN=2235-2988

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