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

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

doi:10.3389/fcimb.2021.642658

Abstract

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.

Highlights

Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota (Kwon-Chung and Bennett, 1992; Maziarz and Perfect, 2016)
The primary objectives of this study were to evaluate the pathogenic features and antifungal susceptibility of Cryptococcus-related genera isolated from pigeon droppings, compared to the Cryptococcus gattii/ neoformans species complex strains obtained from clinical samples of patients belonging to 3 different Brazilian states (Bahia, Pernambuco and Rio Grande do Norte) in the Northeast region
The average value of P. laurentii strains for phospholipase production was considered lower than the results found for N. liquefasciens/N. albidosimilis and N. adeliensis/N. albidastrains (P

Summary

Introduction

Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota (Kwon-Chung and Bennett, 1992; Maziarz and Perfect, 2016). Cryptococcus spp., such as the Cryptococcus gattii/ neoformans species complex, are able to enter mammalian hosts and cause damage to the central nervous system (CNS) (Kwon-Chung et al, 2014; Lakoh et al, 2020) and respiratory tract (Lakoh et al, 2020). Besides HIV/AIDS infection, other risk factors for cryptococcosis include corticosteroids and other immunosuppressive therapies, solid organ transplantation, malignant and rheumatological diseases (Maziarz and Perfect, 2016). Hagen et al (2015) recognized multiple species within the Cryptococcus gattii/neoformans species complex, including the existence of four C. neoformans genotypes: VNI and VNII A new C. gattii molecular type has been discovered in the African environments of the Central Miombo Woodlands (VGV) (Farrer et al, 2019)

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