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Cryptococcus neoformans is a lethal human fungal pathogen and copper has been suggested to be important for virulence.Recent studies demonstrated that Cryptococcus cells sense elevated copper levels in the lung, and the copper detoxification metallothioneins are essential for fungal survival and virulence.In the present work, we characterized the function of Cu transporters in fungal virulence.We demonstrated that Cryptococcus Cu transporters differentially influence fungal survival during pulmonary infection and the onset of meningoencephalitis.