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二氢叶酸还原酶的过量产生导致酵母对磺胺二氢蝶酸产生抗性。

Over-production of dihydrofolate reductase leads to sulfa-dihydropteroate resistance in yeast.

作者信息

Patel Onisha, Karnik Kuldeep, Macreadie Ian G

机构信息

CSIRO Health Sciences and Nutrition, Parkville, Vic., Australia.

出版信息

FEMS Microbiol Lett. 2004 Jul 15;236(2):301-5. doi: 10.1016/j.femsle.2004.06.001.

Abstract

Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP. The effect of over-production of DHFR on sulfa-DHP resistance was examined in Saccharomyces cerevisiae using a strain that requires DHF for growth. This strain was transformed with a plasmid which encodes over-production of DHFR in the presence of CuSO4. Over-production led to resistance to sulfa-DHP suggesting that sulfa-DHP targets DHFR. Spontaneous mutants hyper-resistant to sulfa-DHP did not show any changes within DHFR.

摘要

二氢蝶酸合酶(DHPS)可将磺胺类药物代谢为磺胺二氢蝶酸(sulfa-DHP),后者通过与二氢叶酸(DHF)竞争来抑制细胞生长,这可能表明二氢叶酸还原酶(DHFR)是sulfa-DHP的作用靶点。使用一株生长需要DHF的酿酒酵母菌株,研究了DHFR过量表达对sulfa-DHP抗性的影响。该菌株用一种在硫酸铜存在下编码DHFR过量表达的质粒进行转化。过量表达导致对sulfa-DHP产生抗性,表明sulfa-DHP的作用靶点是DHFR。对sulfa-DHP具有高度抗性的自发突变体在DHFR内未显示任何变化。

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