...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Antimicrobial agents and chemotherapy. >Pseudomonas aeruginosa reveals high intrinsic resistance to penem antibiotics: penem resistance mechanisms and their interplay.
【24h】

Pseudomonas aeruginosa reveals high intrinsic resistance to penem antibiotics: penem resistance mechanisms and their interplay.

机译：铜绿假单胞菌对青霉素类抗生素表现出很高的内在抗性：青霉菌抗性机制及其相互作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pseudomonas aeruginosa exhibits high intrinsic resistance to penem antibiotics such as faropenem, ritipenem, AMA3176, sulopenem, Sch29482, and Sch34343. To investigate the mechanisms contributing to penem resistance, we used the laboratory strain PAO1 to construct a series of isogenic mutants with an impaired multidrug efflux system MexAB-OprM and/or impaired chromosomal AmpC beta-lactamase. The outer membrane barrier of PAO1 was partially eliminated by inducing the expression of the plasmid-encoded Escherichia coli major porin OmpF. Susceptibility tests using the mutants and the OmpF expression plasmid showed that MexAB-OprM and the outer membrane barrier, but not AmpC beta-lactamase, are the main mechanisms involved in the high intrinsic penem resistance of PAO1. However, reducing the high intrinsic penem resistance of PAO1 to the same level as that of penem-susceptible gram-negative bacteria such as E. coli required the loss of either both MexAB-OprM and AmpC beta-lactamase or both MexAB-OprM and the outer membrane barrier. Competition experiments for penicillin-binding proteins (PBPs) revealed that the affinity of PBP 1b and PBP 2 for faropenem were about 1.8- and 1.5-fold lower, than the respective affinity for imipenem. Loss of the outer membrane barrier, MexAB, and AmpC beta-lactamase increased the susceptibility of PAO1 to almost all penems tested compared to the susceptibility of the AmpC-deficient PAO1 mutants to imipenem. Thus, it is suggested that the high intrinsic penem resistance of P. aeruginosa is generated from the interplay among the outer membrane barrier, the active efflux system, and AmpC beta-lactamase but not from the lower affinity of PBPs for penems.
机译：铜绿假单胞菌对诸如法罗培南，利替培南，AMA3176，舒洛培南，Sch29482和Sch34343等青霉素类抗生素表现出很高的内在抗性。为研究促成青霉菌抗性的机制，我们使用实验室菌株PAO1构建了一系列同基因突变体，其多药外排系统MexAB-OprM和/或染色体AmpCβ-内酰胺酶均受损。通过诱导质粒编码的大肠杆菌主要孔蛋白OmpF的表达，部分消除了PAO1的外膜屏障。使用该突变体和OmpF表达质粒的药敏试验表明，MexAB-OprM和外膜屏障（而不是AmpCβ-内酰胺酶）是PAO1高内在青霉素抗性的主要机制。但是，要将PAO1的高固有Penem耐药性降低到与对Penem敏感的革兰氏阴性细菌（如大肠杆菌）相同的水平，则需要同时失去MexAB-OprM和AmpCβ-内酰胺酶或MexAB-OprM和外膜屏障。青霉素结合蛋白（PBP）的竞争实验表明，PBP 1b和PBP 2对法罗培南的亲和力比对亚胺培南的亲和力分别低1.8倍和1.5倍。与缺乏AmpC的PAO1突变株对亚胺培南的敏感性相比，外膜屏障，MexAB和AmpCβ-内酰胺酶的丧失增加了PAO1对几乎所有测试的Penem的敏感性。因此，表明铜绿假单胞菌的高固有内在抗青霉病性是由外膜屏障，活性外排系统和AmpCβ-内酰胺酶之间的相互作用产生的，而不是由PBP对青霉病的较低亲和力产生的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号