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 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 microg/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.
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J D
JD
Nosanchuk
R
R
Ovalle
A
A
Casadevall
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000472:pathogenicity; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D042845:Laccase; D007980:Levodopa / Q000494:pharmacology; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D000097797:Glyphosate
D000935:Antifungal Agents; D004837:Epinephrine; D005998:Glycine; D042845:Laccase; D007980:Levodopa; D008543:Melanins; D010088:Oxidoreductases; D000097797:Glyphosate