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Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence.
Black, Braydon; da Silva, Leandro Buffoni Roque; Hu, Guanggan; Qu, Xianya; Smith, Daniel F Q; Magaña, Armando Alcázar; Horianopoulos, Linda C; Caza, Mélissa; Attarian, Rodgoun; Foster, Leonard J; Casadevall, Arturo; Kronstad, James W.
Afiliación
  • Black B; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • da Silva LBR; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Hu G; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Qu X; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Smith DFQ; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Magaña AA; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Horianopoulos LC; Metabolomics Core Facility, Life Sciences Institute, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Caza M; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Attarian R; Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, USA.
  • Foster LJ; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Casadevall A; Larissa Yarr Medical Microbiology Laboratory, Kelowna General Hospital, Kelowna, British Columbia, Canada.
  • Kronstad JW; The Michael Smith Laboratories, Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Nat Microbiol ; 9(8): 2084-2098, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38956248
ABSTRACT
The fungal pathogen Cryptococcus neoformans is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How C. neoformans manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxidación-Reducción / Criptococosis / Cryptococcus neoformans / Glutatión / Macrófagos / Melaninas Límite: Animals Idioma: En Revista: Nat Microbiol Año: 2024 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxidación-Reducción / Criptococosis / Cryptococcus neoformans / Glutatión / Macrófagos / Melaninas Límite: Animals Idioma: En Revista: Nat Microbiol Año: 2024 Tipo del documento: Article País de afiliación: Canadá