Braydon Black, Leandro Buffoni Roque da Silva, Guanggan Hu, Xianya Qu, Daniel F. Q. Smith, Armando Alcázar Magaña, Linda C. Horianopoulos, Mélissa Caza, Rodgoun Attarian, Leonard J. Foster, Arturo Casadevall, James W. Kronstad
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引用次数: 0
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. Glutathione metabolism in Cryptococcus neoformans influences the redox environment and melanin production, and thus affects fungal virulence.
期刊介绍:
Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes:
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Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation.
In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.