Cryptococcus neoformans methionine synthase:: expression analysis and requirement for virulence
Cryptococcus neoformans methionine synthase:: expression analysis and requirement for virulence
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DOI：
10.1099/mic.0.27235-0
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发表时间：
2004-09-01
期刊：
影响因子：
2.8
通讯作者：
McCusker, JH
中科院分区：
文献类型：
--
作者：
Pascon, RC;Ganous, TM;McCusker, JH
本文描述了甲硫氨酸合成酶基因（MET 6）在人类病原真菌新生隐球菌中的表达谱和一种新型隐球菌的表型。neoformans met6突变体。与MET 3基因相反，MET 3基因在测试的任何环境条件下均未显示出显著的表达变化，MET 6基因显示出响应于甲硫氨酸的显著诱导和响应于高半胱氨酸的显著转录诱导。与met3突变体一样，met6突变体是甲硫氨酸营养缺陷型。然而，相对于met3突变体，met6突变体生长非常缓慢，耐热性较差。与met3突变体相反，met6突变体在缺乏甲硫氨酸时失去活力，并且缺乏荚膜形成。与met3突变体一样，met6突变体是无毒的。与met3突变体相反，met6突变体对氟康唑和钙调磷酸酶抑制剂FK 506和环孢菌素A过敏。在这些药物中的每一种与met6之间也发现了协同杀真菌作用。met3和met6突变体之间的表型差异可能是由于在met6突变体中高半胱氨酸的积累，高半胱氨酸是抑制甾醇生物合成的毒性代谢中间体。
This paper describes (i) the expression profile of the methionine synthase gene (MET6) in the human pathogenic fungus Cryptococcus neoformans and (ii) the phenotypes of a C. neoformans met6 mutant. In contrast to the MET3 gene, which showed no significant change in expression in any environmental condition tested, the MET6 gene showed a substantial induction in response to methionine and a dramatic transcriptional induction in response to homocysteine. Like a met3 mutant, the met6 mutant was a methionine auxotroph. However, relative to a met3 mutant, the met6 mutant grew very slowly and was less heat-shock resistant. In contrast to a met3 mutant, the met6 mutant lost viability when starved of methionine, and it was deficient in capsule formation. Like a met3 mutant, the met6 mutant was avirulent. In contrast to a met3 mutant, the met6 mutant was hypersensitive to fluconazole and to the calcineurin inhibitors FK506 and cyclosporin A. A synergistic fungicidal effect was also found between each of these drugs and met6. The phenotypic differences between the met3 and met6 mutants may be due to the accumulation in met6 mutants of homocysteine, a toxic metabolic intermediate that inhibits sterol biosynthesis.