2010年至2015年间中国上海志贺氏菌分离株中的氟喹诺酮耐药机制
Fluoroquinolone Resistance Mechanisms in Shigella Isolates in Shanghai, China, Between 2010 and 2015.
作者信息
Zhang Wen-Xia, Chen Hong-You, Tu Li-Hong, Xi Man-Fang, Chen Min, Zhang Jue
机构信息
1 Department of Clinical Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai, China .
2 Laboratory of Bacterial, Shanghai Center for Disease Control and Prevention , Shanghai, China .
出版信息
Microb Drug Resist. 2019 Mar;25(2):212-218. doi: 10.1089/mdr.2018.0113. Epub 2018 Oct 10.
OBJECTIVES
This study aimed to investigate the antimicrobial susceptibility of Shigella isolated in Shanghai, China and to determine the genetic basis of its resistance to fluoroquinolones.
MATERIALS AND METHODS
A total of 402 strains of Shigella, including 145 Shigella flexneri and 257 Shigella sonnei isolates, were analyzed. The Kirby-Bauer disk diffusion method was used to determine the susceptibility of the strains to 13 antimicrobials. Minimum inhibitory concentration of ciprofloxacin was determined by E-test. Mutations within the quinolone resistance-determining regions (QRDRs) of gyrA and parC and in the plasmid-mediated quinolone resistance (PMQR) genes, including qnrA, qnrB, qnrS, and aac (6')-Ib-cr, were detected by polymerase chain reaction. All the products were then sequenced.
RESULTS
Most of the Shigella isolates were found to be resistant to nalidixic acid (96.4%), streptomycin (96.4%), ampicillin (86.2%), tetracycline (79.8%), and sulfamethoxazole/trimethoprim (80.6%). S. flexneri isolates showed a significantly higher resistance to cefepime (33.6%), ciprofloxacin (54.2%), norfloxacin (34.1%), and levofloxacin (12.1%) compared with that observed for the S. sonnei strains (χ analysis, p < 0.05). Three mutations (Ser83, Asp87, and His211) in gyrA and one mutation (Ser80) in parC were detected. Of 257 S. sonnei isolates, 11.7% possessed gyrA mutations and 2% had parC mutations. Of 145 S. flexneri isolates, 98.6% possessed gyrA mutations and 97.9% had parC mutations. The plasmid-mediated resistance genes of qnrS and aac (6')-Ib-cr were detected among 17 strains (4.2%).
CONCLUSIONS
The mutation percentage within the QRDR of S. flexneri was as high as 98.6 in gyrA and 97.9 in parC. The significant abundance of mutations within QRDRs conferred high levels of fluoroquinolone resistance. Moreover, the PMQR genes, particularly qnrS, played an important role in the decreased susceptibility of Shigella to fluoroquinolones.
目的
本研究旨在调查中国上海分离出的志贺氏菌的抗菌药敏性，并确定其对氟喹诺酮类耐药的遗传基础。
材料与方法
共分析了402株志贺氏菌，其中包括145株福氏志贺氏菌和257株宋内志贺氏菌。采用 Kirby-Bauer 纸片扩散法测定这些菌株对13种抗菌药物的敏感性。通过 E-test 法测定环丙沙星的最低抑菌浓度。通过聚合酶链反应检测gyrA和parC喹诺酮耐药决定区（QRDRs）以及质粒介导的喹诺酮耐药（PMQR）基因（包括qnrA、qnrB、qnrS和aac(6')-Ib-cr）内的突变。所有产物随后进行测序。
结果
大多数志贺氏菌分离株对萘啶酸（96.4%）、链霉素（96.4%）、氨苄西林（86.2%）、四环素（79.8%）和磺胺甲恶唑/甲氧苄啶（80.6%）耐药。与宋内志贺氏菌菌株相比，福氏志贺氏菌分离株对头孢吡肟（33.6%）、环丙沙星（54.2%）、诺氟沙星（34.1%）和左氧氟沙星（12.1%）的耐药性显著更高（χ分析，p<0.05）。检测到gyrA中的三个突变（Ser83、Asp87和His211）和parC中的一个突变（Ser80）。在257株宋内志贺氏菌分离株中，11.7%存在gyrA突变，2%存在parC突变。在145株福氏志贺氏菌分离株中，98.6%存在gyrA突变，97.9%存在parC突变。在17株（4.2%）菌株中检测到质粒介导的耐药基因qnrS和aac(6')-Ib-cr。
结论
福氏志贺氏菌QRDR内gyrA的突变率高达98.6%，parC的突变率高达97.9%。QRDRs内大量的突变导致高水平的氟喹诺酮耐药性。此外，PMQR基因，尤其是qnrS，在志贺氏菌对氟喹诺酮类药物敏感性降低中起重要作用。
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