Title:	Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis
Authors:	Sousa, Herdson Renney de Oliveira Jr, Getúlio Pereira de Frazão, Stefânia de Oliveira Gorgonha, Kaio César de Melo Rosa, Camila Pereira Garcez, Emãnuella Melgaço Lucas Jr, Joaquim Correia, Amabel Fernandes Freitas, Waleriano Ferreira de Borges, Higor Matos Alves, Lucas Gomes de Brito Paes, Hugo Costa Trilles, Luciana Lazera, Márcia dos Santos Teixeira, Marcus de Melo Pinto Jr, Vitor Laerte Felipe, Maria Sueli Soares Casadevall, Arturo Silva-Pereira, Ildinete Albuquerque, Patrícia Nicola, André Moraes
Affilliation:	University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. Harvard Medical School. Beth Israel Deaconess Medical Center. Department of Medicine. Division of Allergy and Inflammation. Boston, MA, USA. University of Brasília. Institute of Biological Sciences. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. Fundação Oswaldo Cruz. Brasília, DF, Brazil. Central Public Health Laboratory. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Micologia. Rio de Janeiro, RJ, Brasil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil. Fundação Oswaldo Cruz. Brasília, DF, Brazil. Catholic University of Brasília. Graduate Program in Genomic Sciences and Biotechnology. Brasília, DF, Brazil. Johns Hopkins Bloomberg School of Public Health. Department of Molecular Microbiology and Immunology. Baltimore, MD, USA. University of Brasília. Institute of Biological Sciences. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil. University of Brasília. Institute of Biological Sciences. Laboratory of Molecular Biology of Pathogenic Fungi. Brasília, DF, Brazil / University of Brasília. Faculty of Ceilândia. Brasília, DF, Brazil. University of Brasília. Faculty of Medicine. Brasília, DF, Brazil / Catholic University of Brasília. Graduate Program in Genomic Sciences and Biotechnology. Brasília, DF, Brazil.
Abstract:	Cryptococcus spp. are human pathogens that cause 181,000 deaths per year. In this work, we systematically investigated the virulence attributes of Cryptococcus spp. clinical isolates and correlated them with patient data to better understand cryptococcosis. We collected 66 C. neoformans and 19 C. gattii clinical isolates and analyzed multiple virulence phenotypes and host-pathogen interaction outcomes. C. neoformans isolates tended to melanize faster and more intensely and produce thinner capsules in comparison with C. gattii. We also observed correlations that match previous studies, such as that between secreted laccase and disease outcome in patients. We measured Cryptococcus colony melanization kinetics, which followed a sigmoidal curve for most isolates, and showed that faster melanization correlated positively with LC3-associated phagocytosis evasion, virulence in Galleria mellonella and worse prognosis in humans. These results suggest that the speed of melanization, more than the total amount of melanin Cryptococcus spp. produces, is crucial for virulence.
Keywords:	Cryptococcus neoformans Galleria mellonella LC3-associated phagocytosis Capsule Cryptococcosis Extracellular vesicles Melanin Virulence
Issue Date:	2022
Publisher:	MDPI
Citation:	SOUSA, Herdson Renney et al. Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis. Journal of fungi, v. 8, n. 4, p. 1-20, 2022
DOI:	10.3390/jof8040393
ISSN:	2309-608X
Copyright:	open access
Appears in Collections:	INI - Artigos de Periódicos

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