Gene amplification contributes to sulfonamide resistance in Escherichia coli.
Gene amplification contributes to sulfonamide resistance in Escherichia coli.
复制标题
基因扩增导致大肠杆菌对磺胺类药物产生耐药性。
DOI：
10.1128/aac.33.12.2042
复制
发表时间：
1989
影响因子：
4.9
通讯作者：
Guay,GG
中科院分区：
文献类型：
--
作者：
Nichols,BP;Guay,GG
一个磺胺噻唑耐药菌株的大肠杆菌被分离出来，并显示含有一个四倍的串联扩增的DNA 18个酶对长度的片段，除了突变改变的二氢蝶酸合酶，磺胺抑制的靶酶。扩增的DNA含有一个名为sur的基因，当该基因比野生型中的基因含量更高时，该基因有助于磺胺噻唑抗性。非选择性生长后，扩增DNA丢失后，磺胺噻唑抗性显著降低。含有sur的质粒也仅赋予野生型菌株较弱的磺胺噻唑抗性。扩增DNA、野生型DNA和含sur-containing质粒的限制性酶切图谱的比较表明，DNA重排发生在DNA扩增事件之前或伴随DNA扩增事件。DNA重排导致从一个IS 5插入，这与一个IS 5元件居住在野生型菌株的表面附近，导致在一个-IS 5-sur-IS 5-配置。同源重组可以解释sur区域的重复和随后的扩增。高拷贝数的质粒含有苏尔基因座不表达抗磺胺噻唑二氢蝶酸合酶，也没有过表达野生型二氢蝶酸合酶。这些数据表明，该菌株中的高水平的磺胺噻唑耐药性是由两种不同突变的协同效应引起的。
A sulfathiazole-resistant strain of Escherichia coli was isolated and shown to contain a fourfold tandemly amplified segment of DNA 18 kilobase pairs in length in addition to a mutationally altered dihydropteroate synthase, the target enzyme for sulfonamide inhibition. The amplified DNA contained a gene designated sur that contributed to sulfathiazole resistance when present in greater amounts than those in the wild type. Sulfathiazole resistance was markedly decreased upon loss of the amplified DNA after nonselective growth. Plasmids that contained sur also conferred only weak sulfathiazole resistance on wild-type strains. Comparison of the restriction maps of the amplified DNA, wild-type DNA, and sur-containing plasmids showed that a DNA rearrangement occurred before or concomitant with the DNA amplification event. The DNA rearrangement resulted from an IS5 insertion, which, in conjunction with an IS5 element residing near sur in the wild-type strain, resulted in an -IS5-sur-IS5- configuration. Homologous recombination could account for duplication and subsequent amplification of the sur region. High-copy-number plasmids containing the sur locus did not express a sulfathiazole-resistant dihydropteroate synthase, nor did they overexpress wild-type dihydropteroate synthase. These data suggest that the high level of sulfathiazole resistance in this strain results from a synergistic effect of two different mutations.