TY - JOUR
T1 - Faster Cryptococcus Melanization Increases Virulence in Experimental and Human Cryptococcosis
AU - de Sousa, Herdson Renney
AU - de Oliveira, Getúlio Pereira
AU - Frazão, Stefânia de Oliveira
AU - Gorgonha, Kaio César de Melo
AU - Rosa, Camila Pereira
AU - Garcez, Emãnuella Melgaço
AU - Lucas, Joaquim
AU - Correia, Amabel Fernandes
AU - de Freitas, Waleriano Ferreira
AU - Borges, Higor Matos
AU - de Brito Alves, Lucas Gomes
AU - Paes, Hugo Costa
AU - Trilles, Luciana
AU - Lazera, Márcia Dos Santos
AU - Teixeira, Marcus de Melo
AU - Pinto, Vitor Laerte
AU - Felipe, Maria Sueli Soares
AU - Casadevall, Arturo
AU - Silva-Pereira, Ildinete
AU - Albuquerque, Patrícia
AU - Nicola, André Moraes
N1 - Funding Information:
Funding: A.M.N. was funded by FAP-DF awards 0193.001048/2015-0193.001561/2017 and the CNPq grant 437484/2018-1. M.S.S.F. was supported by FAP-DF/PRONEX award 193.001.533/2016. A.C. was supported by the National Institutes of Health grants 5R01A1033774, 5R37AI033142, and 5T32A107506, and CTSA grants 1 ULI TR001073-01, 1 TLI 1 TR001072-01, and 1 KL2 TR001071 from the National Center for Advancing Translational Sciences. The article publishing charges (APC) were funded by the University of Brasília.
Funding Information:
A.M.N. was funded by FAPDF awards 0193.001048/2015-0193.001561/2017 and the CNPq grant 437484/2018-1. M.S.S.F. was supported by FAP-DF/PRONEX award 193.001.533/2016. A.C. was supported by the National Institutes of Health grants 5R01A1033774, 5R37AI033142, and 5T32A107506, and CTSA grants 1 ULI TR001073-01, 1 TLI 1 TR001072-01, and 1 KL2 TR001071 from the National Center for Advancing Translational Sciences. The article publishing charges (APC) were funded by the University of Bras?lia.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Cryptococcus neoformans
KW - Galleria mellonella
KW - LC3-associated phagocytosis
KW - capsule
KW - cryptococcosis
KW - extracellular vesi-cles
KW - melanin
KW - virulence
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U2 - 10.3390/jof8040393
DO - 10.3390/jof8040393
M3 - Article
C2 - 35448624
AN - SCOPUS:85129102648
SN - 2309-608X
VL - 8
JO - Journal of Fungi
JF - Journal of Fungi
IS - 4
M1 - 393
ER -