Promoter deletions of Klebsiella pneumoniae carbapenemase (KPC)-encoding genes (blaKPC -2) and efflux pump (AcrAB) on β-lactam susceptibility in KPC-producing Enterobacteriaceae.
Promoter deletions of Klebsiella pneumoniae carbapenemase (KPC)-encoding genes (blaKPC -2) and efflux pump (AcrAB) on β-lactam susceptibility in KPC-producing Enterobacteriaceae.
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DOI：
10.1111/1574-6968.12273
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发表时间：
2013-11
影响因子：
2.1
通讯作者：
Kwon DH
中科院分区：
文献类型：
--
作者：
Seecoomar GD;Marmol BC;Kwon DH
肺炎克雷伯菌碳青霉烯酶(KPC)编码基因(blaKPC-2a、blaKPC-2b和blaKPC-2c)广泛存在于肠杆菌科细菌中。临床产β的肠杆菌科细菌对KpC-内酰胺类抗生素的最低抑菌浓度(MIC)从敏感到高度耐药，导致诊断问题。为了更好地了解产β的肠杆菌科细菌对β-内酰胺类药物敏感性的差异，用blaKPC-2基因的3种异构体转化大肠杆菌W4573及其外排泵缺失突变株，研究其对KpC-内酰胺类抗生素敏感性的影响。BLAKPC-2a、BLAKPC-2b和BLAKPC-2c转化子对β-内酰胺类抗生素的最低抑菌浓度(MIC)分别是单独克隆载体的1~500倍。然而，除氨曲南和羧苯西林外，acrAB突变株的转化子仍然对所有测试的β-内酰胺类药物敏感。在含有blaKPC-2a、blaKPC-2b和blaKPC-2c的转化子中，三个启动子的长度和碳青霉烯酶活力的水平与大肠杆菌W4573及其外排泵突变体(AcrAB)中β-内酰胺类物质的水平相关。总之，这些结果表明，在产KpC的肠杆菌科细菌中，blaKPC-2基因和acrAB启动子的缺失可能与β-内酰胺类MIC的变异有关。
Klebsiella pneumoniae carbapenemase (KPC)-encoding genes containing promoter-deletions (blaKPC-2a, blaKPC-2b, and blaKPC-2c) have disseminated in Enterobacteriaceae. The minimal inhibitory concentrations (MICs) to β-lactams in clinical KPC-producing Enterobacteriaceae are ranging from susceptible to high-level resistant resulting in diagnostic problems. In order to better understand the variability in β-lactam MICs among KPC-producing Enterobacteriaceae, three isoforms of blaKPC-2 gene were used to transform E. coli W4573 and its deletion mutant of an efflux pump (AcrAB) to examine the effects on β-lactam susceptibility. MICs to β-lactams in E. coli W4573 and its acrAB mutant strain increased 1- to 500-fold (MIC from 0.125 to 64 µg/mL of aztreonam) in the blaKPC-2a, blaKPC-2b, and blaKPC-2c transformants compared with the cloning vector alone. However, transformants of the acrAB mutant strain remained susceptible to all β-lactams tested except for aztreonam and carbenicillin. Levels of the three promoters’ length and carbapenemase activities in the transformants harboring the blaKPC-2a, blaKPC-2b, and blaKPC-2c were correlated to the levels of β-lactam MICs in both E. coli W4573 and its mutant of an efflux pump (AcrAB). Overall, these results suggest that promoter-deletions of blaKPC-2 gene and AcrAB may be associated with the variability in β-lactam MICs in KPC-producing Enterobacteriaceae.
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影响因子：
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