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FASTER CRYPTOCOCCUS MELANIZATION INCREASES VIRULENCE IN EXPERIMENTAL AND HUMAN CRYPTOCOCCOSIS
Sousa, Herdson Renney de et al. | Date Issued: 2022
Author
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. Fiocruz Brasília. 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. Fiocruz Brasília. 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
 
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