Glyphosate inhibits melanization of Cryptococcus neoformans and prolongs survival of mice after systemic infection

Cryptococcus neoformans is a major fungal pathogen and is a relatively comm on cause of life-threatening meningoencephalitis. Glyphosate is a widely us ed herbicide that inhibits the synthesis of aromatic amino acids via the sh ikimate acid pathway. This study investigated the effects of glyphosate on C. neoformans growth, melanization, and murine infection. C. neoformans was relatively resistant to glyphosate, requiring concentrations >250 mg/mL fo r inhibition. Melanization of C. neoformans in the presence of L-dopa was i nhibited by subinhibitory concentrations of glyphosate. Glyphosate inhibite d autopolymerization of L-dopa and oxidation of L-epinephrine by cryptococc al cells, which is mediated by a laccase. Administration of glyphosate to m ice infected with C. neoformans delayed melanization of yeast cells in vivo and prolonged average mouse survival. The results suggest that inhibition of melanization in vivo may facilitate control of C. neoformans infection.