Faster Melanization Increases Virulence in Experimental and Human Cryptococcosis

spp. are human pathogens that cause 181,000 deaths per year. In this work, we systematically investigated the virulence attributes of spp. clinical isolates and correlated them with patient data to better understand cryptococcosis. We collected 66 and 19 clinical isolates and analyzed multiple virulence phenotypes and host-pathogen interaction outcomes. isolates tended to melanize faster and more intensely and produce thinner capsules in comparison with . We also observed correlations that match previous studies, such as that between secreted laccase and disease outcome in patients. We measured 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 and worse prognosis in humans. These results suggest that the speed of melanization, more than the total amount of melanin spp. produces, is crucial for virulence.

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