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Antimicrobial Agents and Chemotherapy, November 2007, p. 4105-4110, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00616-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prevalence and Expression of the Plasmid-Mediated Quinolone Resistance Determinant qnrA1{triangledown}

Xiaogang Xu,1 Shi Wu,1 Xinyu Ye,1 Yang Liu,1 Wanliang Shi,1 Yingyuan Zhang,1 and Minggui Wang1,2*

Institute of Antibiotics, Huashan Hospital,1 Institute of Biomedical Sciences, Fudan University, Shanghai 200040, People's Republic of China2

Received 10 May 2007/ Returned for modification 2 July 2007/ Accepted 16 August 2007

Since its discovery, qnrA has been found in most common Enterobacteriaceae. Ciprofloxacin MICs conferred by different qnrA-positive plasmids could range from 0.1 µg/ml to 2 µg/ml in Escherichia coli J53. The reasons for different ciprofloxacin MICs conferred by qnrA have not been fully clarified. Five hundred forty-one consecutive gram-negative clinical strains that were resistant or intermediate to ciprofloxacin and that were isolated in Shanghai in 2005 were screened for qnrA by PCR. For qnrA-positive isolates, the transferability of quinolone resistance was determined by conjugation and mutations within the quinolone resistance-determining region (QRDR) of gyrA and parC. aac(6')-Ib-cr was detected and qnrA RNA expression was determined using real-time reverse transcription-PCR for transconjugants with different ciprofloxacin MICs. The qnrA gene was detected in 7 of the 541 clinical isolates. Quinolone resistance was transferred in four strains by conjugation. Mutations in the QRDR of gyrA and parC were detected in five qnrA-positive clinical strains with higher ciprofloxacin MICs. Of four qnrA-bearing plasmids in E. coli J53, pHS4 and pHS5 conferred ciprofloxacin MICs of 0.094 to 0.125 µg/ml; pHS3, which harbored the aac(6')-Ib-cr gene as well, conferred a ciprofloxacin MIC of 0.25 µg/ml, and pHS6, which had both the aac(6')-Ib-cr gene and a high expression level of qnrA, had a ciprofloxacin MIC of 1.0 µg/ml. The prevalence of qnrA appeared to be higher in Enterobacter cloacae than in other Enterobacteriaceae. The coexistence of qnrA and aac(6')-Ib-cr in a single plasmid and increased qnrA expression can account for the different levels of ciprofloxacin resistance seen in transconjugants.

* Corresponding author. Mailing address: Institute of Antibiotics, Huashan Hospital, Fudan University, 12 M. Wulumuqi Rd., Shanghai 200040, People's Republic of China. Phone: (86-21)-62489999, ext. 6507. Fax: (86-21)-62488290. E-mail: mgwang{at}fudan.edu.cn

{triangledown} Published ahead of print on 27 August 2007.

Antimicrobial Agents and Chemotherapy, November 2007, p. 4105-4110, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00616-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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