Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species
Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species
复制标题
脲原体物种中频繁的拓扑异构酶 IV 突变与氟喹诺酮耐药相关。
DOI：
10.1099/jmm.0.000153
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发表时间：
2015-11-01
影响因子：
3
通讯作者：
Xie, Xinyou
中科院分区：
文献类型：
--
作者：
Song, Jingjuan;Qiao, Yingli;Xie, Xinyou
本研究旨在探讨DNA促旋酶（gyrA和gyrB编码）和拓扑异构酶IV（parC和帕雷编码）的喹诺酮类耐药决定区（QRDRs）在氟喹诺酮类药物耐药中的作用。共检出114株脲原体属（Ureplasma spp.）从临床女性有症状感染患者中分离的菌株进行了种属分布和对4种氟喹诺酮类药物的敏感性测试。此外，我们分析了QRDR，并将其与14种脲原体属ATCC参考菌株进行了比较。血清型，以确定导致抗菌素耐药性的突变。我们的研究表明，氟喹诺酮类药物对脲原体最有效。(MIC范围：0.125-32 μg/ml）。然而，环丙沙星（MIC范围：1-256 μg ml）和氧氟沙星（MIC范围：0.5-128 μg ml）的MIC估计值极高，其次是左氧氟沙星（MIC范围：0.5-64 μg ml）。在GyrB、ParC和帕雷中发现了7个氨基酸替换，而在GyrA中没有发现。ParC区Ser-83 → Leu/Trp（C248 T/G）和ParE区Arg-448 → Lys（G1343 A）分别为89株（77.2%）和3株（2.6%）。 GyrB中Pro-462 → Ser（C1384 T）、Asn-481 → Ser（A1442 G）和Ala-493 →瓦尔（C1478 T）和ParC中Met-105 → Ile（G315 T）为中性多态性，且与ParC中Ser-83 → Leu（C248 T）的氨基酸变化沿着发生。有趣的是，在四个菌株中独立地发现了ParC和帕雷的两个新突变。提示拓扑异构酶IV的氨基酸突变可能是导致耐药的主要原因，尤其是ParC中Ser-83 → Leu（C248 T）突变。莫西沙星对Ser-83 → Leu突变菌株的抗菌活性最好。
This study aimed to investigate the role of quinolone resistance-determining regions (QRDRs) of DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE) associated with fluoroquinolone resistance. A total of 114 Ureaplasma spp. strains, isolated from clinical female patients with symptomatic infection, were tested for species distribution and susceptibility to four fluoroquinolones. Moreover, we analysed the QRDRs and compared these with 14 ATCC reference strains of Ureaplasma spp. serovars to identify mutations that caused antimicrobial resistance. Our study indicated that moxifloxacin was the most effective fluoroquinolone against Ureaplasma spp. (MIC range: 0.125-32 μg ml⁻¹). However, extremely high MICs were estimated for ciprofloxacin (MIC range: 1-256 μg ml⁻¹) and ofloxacin (MIC range: 0.5-128 μg ml⁻¹), followed by levofloxacin (MIC range: 0.5-64 μg ml⁻¹). Seven amino acid substitutions were discovered in GyrB, ParC and ParE, but not in GyrA. Ser-83 → Leu/Trp (C248T/G) in ParC and Arg-448 → Lys (G1343A) in ParE, which were potentially responsible for fluoroquinolone resistance, were observed in 89 (77.2 %) and three (2.6 %) strains, respectively. Pro-462 → Ser (C1384T), Asn-481 → Ser (A1442G) and Ala-493 → Val (C1478T) in GyrB and Met-105 → Ile (G315T) in ParC seemed to be neutral polymorphisms, and were observed and occurred along with the amino acid change of Ser-83 → Leu (C248T) in ParC. Interestingly, two novel mutations of ParC and ParE were independently found in four strains. These observations suggest that amino acid mutation in topoisomerase IV appears to be the leading cause of fluoroquinolone resistance, especially the mutation of Ser-83 → Leu (C248T) in ParC. Moxifloxacin had the best activity against strains with Ser-83 → Leu mutation.