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Exposure to Sublethal Ciprofloxacin Induces Resistance to Ciprofloxacin and Cross-Antibiotics, and Reduction of Fitness, Biofilm Formation, and Apx Toxin Secretion in Actinobacillus pleuropneumoniae

文献类型： 外文期刊

作者： Guo, Fangfang 1 ; Guo, Jie 1 ; Cui, Yifang 1 ; Cao, Xiaoya 1 ; Zhou, Hongzhuan 1 ; Su, Xia 1 ; Yang, Bing 1 ; Blackall, P 1 ;

作者机构： 1.Beijing Acad Agr & Forestry Sci, Inst Anim Husb & Vet Med, Beijing Key Lab Prevent & Control Infect Dis Live, 9 Shuguang Huayuan Middle Rd, Beijing 100097, Peoples R China

2.Univ Queensland, Queensland Alliance Agr & Food Innovat, St Lucia, Qld, Australia

关键词： Actinobacillus pleuropneumoniae; ciprofloxacin-resistant mutants; antibiotics resistance; bacterial fitness; biofilm; Apx toxin

期刊名称：MICROBIAL DRUG RESISTANCE （ 影响因子：2.296； 五年影响因子：2.297 ）

ISSN： 1076-6294

年卷期：

页码：

收录情况： SCI

摘要： Actinobacillus pleuropneumoniae, the etiological agent of porcine pleuropneumonia, is increasingly resistant to antibiotics. However, little is known about the mechanisms of antibiotic resistance in this pathogen. In this study, we experimentally evolved the reference strain of both A. pleuropneumoniae serovar 1 and serovar 7, the most prevalent serovars worldwide, to quinolone resistance by sequential exposure to subinhibitory concentrations of ciprofloxacin. The adaptive ciprofloxacin-resistant mutants of A. pleuropneumoniae serovar 1 and serovar 7 had a minimum inhibitory concentration (MIC) increment from 0.004 to 1 or 2 mu g/mL, respectively. Adaptation to ciprofloxacin was shown to confer quinolone resistance with a 32- to 512-fold increase (serovars 1 and 7, respectively) as well as cross-resistance to ampicillin with an increased MIC by 16,384- and 64-fold (serovars 1 and 7, respectively). The genetic analysis of quinolone resistance-determining region mutations showed that substitutions occurred in gyrA (S83A) and parC (D84N) of serovar 1, and gyrA (D87N) of serovar 7. The ciprofloxacin-resistant mutants showed significantly reduced bacterial fitness. The mutants also showed changes in efflux ability and biofilm formation. Notably, the transcription and secretion levels of Apx toxins were dramatically reduced in ciprofloxacin-resistant mutants compared with their wild-type strains. Altogether, these results demonstrated marked phenotypic changes in ciprofloxacin-resistant mutants of A. pleuropneumoniae. The results stress the need for further studies on the impact of both the genotypic and phenotypic characteristics of A. pleuropneumoniae following exposure to subinhibitory concentrations of antibiotics.

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