Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, India.
Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, India.
Microb Pathog. 2019 Jul;132:26-29. doi: 10.1016/j.micpath.2019.04.021. Epub 2019 Apr 16.
Incidence of high fluoroquinolone resistance has been rising rapidly worldwide. Resistance against fluoroquinolones can be either chromosomal or plasmid mediated. Plasmid mediated quinolone resistant(PMQR) genes impart low level of resistance against fluoroquinolones but provides favorable background for selection of additional chromosomally encoded resistance mechanisms. In the natural habitat, conjugal transfer of PMQR genes provides a vehicle for dissemination of fluoroquinolone resistance. Our study indicated successful transmission of PMQR determinants(aac(6')-Ib-cr, qnrA, qnrB, qnrS, oqxB) from ciprofloxacin resistant clinical uropathogenic E.coli(UPEC) isolates to susceptible E.coliJ53Azide-resistant strain in vitro in presence of high ciprofloxacin (5 μg/ml) selection pressure generating transconjugants that exhibited varied MIC(25-800μg/ml) towards the drug with acquired mutations Ser83Leu and Asp87Asn in the quinolone resistant determining regions(QRDR) in gyrA. Therefore this is a first study of its kind that identified high rate of gyrA mutations among transconjugants selected under high ciprofloxacin pressure resulting from bacterial conjugation a common phenomenon in natural habitat along with PMQR gene transmission which imposes a major public health concern.
氟喹诺酮类药物的耐药率在全球范围内迅速上升。氟喹诺酮类药物的耐药性既可以是染色体介导的,也可以是质粒介导的。质粒介导的喹诺酮耐药(PMQR)基因赋予了对氟喹诺酮类药物的低水平耐药性,但为选择额外的染色体编码耐药机制提供了有利的背景。在自然环境中,PMQR 基因的接合转移为氟喹诺酮类耐药的传播提供了一种媒介。我们的研究表明,PMQR 决定因素(aac(6')-Ib-cr、qnrA、qnrB、qnrS、oqxB)能够从耐环丙沙星的临床泌尿道致病性大肠杆菌(UPEC)分离株成功传递到体外对环丙沙星敏感的大肠杆菌 J53Azide 抗性菌株,在高环丙沙星(5μg/ml)选择压力下产生转导子,这些转导子对药物的 MIC(25-800μg/ml)表现出不同的耐药性,其喹诺酮耐药决定区(QRDR)中的gyrA 发生了 Ser83Leu 和 Asp87Asn 获得性突变。因此,这是首次研究在细菌接合这种自然环境中的常见现象以及 PMQR 基因传递的共同作用下,从高环丙沙星压力下选择的转导子中发现 gyrA 突变率高的情况,这对公共卫生构成了重大威胁。