Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates
Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates
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DOI：
10.1128/aac.00665-08
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发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Zechiedrich, Lynn
中科院分区：
文献类型：
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作者：
Morgan-Linnell, Sonia K.;Boyd, Lauren Becnel;Zechiedrich, Lynn
通过编码促旋酶（gyrA和gyrB）和拓扑异构酶IV（parC和帕雷）的基因中获得染色体突变、多药外排泵AcrAB水平增加以及质粒携带基因aac（6 '）-Ib-cr和大肠杆菌中的qnr变体，氟喹诺酮的MIC增加。在随附的报告中，我们发现环丙沙星、加替沙星、左氧氟沙星和诺氟沙星对氟喹诺酮类耐药大肠杆菌的MIC。大肠埃希菌临床分离株的检出率很高，且变异很大（L. Becnel Boyd，M. J. Maynard，S. K.摩根-林内尔湖B。霍顿河，巴西-地苏冈河J. Hamill，J. Rojo Jimenez，J. Versalovic，D. Steffen和L. Zechiedrich，抗微生物剂。探员Chemother 53：229-234，2009）。在这里，我们对gyrA、gyrB、parC和帕雷进行了测序;筛选了aac（6 '）-Ib-cr和qnrA;并定量了大肠杆菌中AcrA的水平。已知患者性别、年龄、位置和感染部位的大肠杆菌分离株。我们发现：（i）所有氟喹诺酮类耐药分离株均存在gyrA突变;（ii）约85%的gyrA突变株也存在parC突变;（iii）环丙沙星和诺氟沙星对携带aac（6 '）-Ib-cr的分离株的MIC（与23%相似），但加替沙星和左氧氟沙星的MIC均不显著升高;和（v）类似于33%的氟喹诺酮耐药分离株AcrA水平升高。AcrA的增加与氟喹诺酮类药物的不敏感性相关，但与医院病历报告的任何其他抗菌药物的不敏感性无关。已知的机制占氟喹诺酮MIC的50 - 70%的分离株;其余包括MIC比预期高1，500倍的分离株。因此，在某些临床分离株中，一定存在其他未知的氟喹诺酮耐药机制。
Fluoroquinolone MICs are increased through the acquisition of chromosomal mutations in the genes encoding gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), increased levels of the multidrug efflux pump AcrAB, and the plasmid-borne genes aac(6')-Ib-cr and the qnr variants in Escherichia coli. In the accompanying report, we found that ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs for fluoroquinolone-resistant E. coli clinical isolates were very high and widely varied (L. Becnel Boyd, M. J. Maynard, S. K. Morgan-Linnell, L. B. Horton, R. Sucgang, R. J. Hamill, J. Rojo Jimenez, J. Versalovic, D. Steffen, and L. Zechiedrich, Antimicrob. Agents Chemother. 53: 229-234, 2009). Here, we sequenced gyrA, gyrB, parC, and parE; screened for aac(6')-Ib-cr and qnrA; and quantified AcrA levels in E. coli isolates for which patient sex, age, location, and site of infection were known. We found that (i) all fluoroquinolone-resistant isolates had gyrA mutations; (ii) similar to 85% of gyrA mutants also had parC mutations; (iii) the ciprofloxacin and norfloxacin MICs for isolates harboring aac(6')-Ib-cr (similar to 23%) were significantly higher, but the gatifloxacin and levofloxacin MICs were not; (iv) no isolate had qnrA; and (v) similar to 33% of the fluoroquinolone-resistant isolates had increased AcrA levels. Increased AcrA correlated with nonsusceptibility to the fluoroquinolones but did not correlate with nonsusceptibility to any other antimicrobial agents reported from hospital antibiograms. Known mechanisms accounted for the fluoroquinolone MICs of 50 to 70% of the isolates; the remaining included isolates for which the MICs were up to 1,500-fold higher than expected. Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates.