Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates
Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates
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DOI：
10.1093/jac/44.6.735
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发表时间：
1999-12-01
影响因子：
5.2
通讯作者：
de Anta, MTJ
中科院分区：
文献类型：
--
作者：
Tavío, MD;Vila, J;de Anta, MTJ
通过将10株临床分离的大肠埃希菌暴露于递增浓度的诺氟沙星和洛美沙星，筛选出18株喹诺酮类耐药大肠埃希菌。突变株表现出多重耐药表型。gyrA基因均为单一突变，其中Ser-83 → Leu（n = 14），瓦尔（n = 1）或Ala（n = 1），Asp-87 → Asn（n = 2）。仅检测到parC中的一个伴随突变（Ser-80-->Arg）。四个亲本分离株在gyrA中表现出单一突变，需要小于或等于1 mg/L的诺氟沙星才能抑制。氟喹诺酮耐药，在18个喹诺酮耐药突变体，是影响DNA旋转酶的突变加上氟喹诺酮摄取减少的结果。后一种耐药机制是缺乏OmpF和增加主动外排在8个分离株，或增加主动外排单独在其余10个选定的突变体的综合效果。
Eighteen quinolone-resistant isolates of Escherichia coli were selected by exposing ten clinical isolates to increasing concentrations of norfloxacin and lomefloxacin. The mutant isolates showed a multiple-antibiotic-resistance phenotype. All of them contained single mutations in gyrA consisting of the substitution of Ser-83-->Leu (n = 14), Val (n = 1) or Ala (n = 1) and the substitution of Asp-87-->Asn (n = 2). Only one concomitant mutation in parC(Ser-80-->Arg) was detected. Four parent isolates exhibited a single mutation in gyrA which required less than or equal to 1 mg/L of norfloxacin to be inhibited. Fluoroquinolone resistance, in the 18 quinolone-resistant mutants, was a result of mutations affecting DNA gyrase plus decreased fluoroquinolone uptake. This latter mechanism of resistance was a combined effect of an absence of OmpF and an increase in active efflux in eight isolates, or an increased active efflux alone in the remaining ten selected mutants.