Nosanchuk J D, Ovalle R, Casadevall A
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Infect Dis. 2001 Apr 1;183(7):1093-9. doi: 10.1086/319272. Epub 2001 Feb 23.
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.
新型隐球菌是一种主要的真菌病原体，是危及生命的脑膜脑炎的相对常见病因。草甘膦是一种广泛使用的除草剂，它通过莽草酸途径抑制芳香族氨基酸的合成。本研究调查了草甘膦对新型隐球菌生长、黑色素形成及小鼠感染的影响。新型隐球菌对草甘膦相对耐药，抑制其生长需要浓度>250μg/mL。亚抑制浓度的草甘膦可抑制新型隐球菌在L-多巴存在下的黑色素形成。草甘膦抑制L-多巴的自聚合以及隐球菌细胞介导的L-肾上腺素氧化，该过程由漆酶介导。给感染新型隐球菌的小鼠施用草甘膦可延迟体内酵母细胞的黑色素形成并延长小鼠平均存活时间。结果表明，体内黑色素形成的抑制可能有助于控制新型隐球菌感染。
