Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis

Herdson Renney de Sousa, Getúlio Pereira de Oliveira, Stefânia de Oliveira Frazão, Kaio César de Melo Gorgonha, Camila Pereira Rosa, Emãnuella Melgaço Garcez, Joaquim Lucas, Amabel Fernandes Correia, Waleriano Ferreira de Freitas, Higor Matos Borges, Lucas Gomes de Brito Alves, Hugo Costa Paes, Luciana Trilles, Márcia Dos Santos Lazera, Marcus de Melo Teixeira, Vitor Laerte Pinto, Maria Sueli Soares Felipe, Arturo Casadevall, Ildinete Silva-Pereira, Patrícia AlbuquerqueAndré Moraes Nicola

Research output: Contribution to journalArticlepeer-review


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 kinet-ics, 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.

Original languageEnglish (US)
Article number393
JournalJournal of Fungi
Issue number4
StatePublished - Apr 2022


  • Cryptococcus neoformans
  • Galleria mellonella
  • LC3-associated phagocytosis
  • capsule
  • cryptococcosis
  • extracellular vesi-cles
  • melanin
  • virulence

ASJC Scopus subject areas

  • Microbiology (medical)
  • Ecology, Evolution, Behavior and Systematics
  • Plant Science


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