TY - JOUR
T1 - Glyphosate inhibits melanization of Cryptococcus neoformans and prolongs survival of mice after systemic infection
AU - Nosanchuk, Joshua Daniel
AU - Ovalle, Rafael
AU - Casadevall, Arturo
N1 - Funding Information:
Financial support: National Institutes of Health (grants AI-22774, AI-13342, and HL-59842 [to A.C.]; AI-01489 [to J.D.N]); Burroughs Wellcome Fund (Scholar Award in Experimental Therapeutics [to A.C]).
PY - 2001/4/1
Y1 - 2001/4/1
N2 - Cryptococcus neoformans is a major fungal pathogen and is a relatively common cause of life-threatening meningoencephalitis. Glyphosate is a widely used herbicide that inhibits the synthesis of aromatic amino acids via the shikimate 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 μg/mL for inhibition. Melanization of C. neoformans in the presence of L-dopa was inhibited by subinhibitory concentrations of glyphosate. Glyphosate inhibited autopolymerization of L-dopa and oxidation of L-epinephrine by cryptococcal cells, which is mediated by a laccase. Administration of glyphosate to mice 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.
AB - Cryptococcus neoformans is a major fungal pathogen and is a relatively common cause of life-threatening meningoencephalitis. Glyphosate is a widely used herbicide that inhibits the synthesis of aromatic amino acids via the shikimate 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 μg/mL for inhibition. Melanization of C. neoformans in the presence of L-dopa was inhibited by subinhibitory concentrations of glyphosate. Glyphosate inhibited autopolymerization of L-dopa and oxidation of L-epinephrine by cryptococcal cells, which is mediated by a laccase. Administration of glyphosate to mice 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.
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U2 - 10.1086/319272
DO - 10.1086/319272
M3 - Article
C2 - 11237835
AN - SCOPUS:0035313294
SN - 0022-1899
VL - 183
SP - 1093
EP - 1099
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -