Chang Man-Xia, Zhang Jin-Fei, Sun Yin-Huan, Li Rong-Sheng, Lin Xiao-Ling, Yang Ling, Webber Mark A, Jiang Hong-Xia
Guangdong Key Laboratory of Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China.
Front Microbiol. 2021 May 6;12:663731. doi: 10.3389/fmicb.2021.663731. eCollection 2021.
Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes ( and ) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in from the food chain.
氟喹诺酮耐药性的产生可能涉及多种机制，包括编码靶标细菌拓扑异构酶的基因（和）中的染色体突变、AcrAB - TolC外排系统表达增加以及获得可传播的喹诺酮耐药基因。在本研究中，收集了176株来自动物的具有广泛环丙沙星最低抑菌浓度（MIC）的分离株，以分析这些不同机制对不同表型的贡献。所有分离株根据其环丙沙星敏感性模式分为以下五组：高度耐药（HR）、耐药（R）、中介（I）、敏感性降低（RS）和敏感（S）。我们发现，ParC T57S替换在环丙沙星MIC最低的菌株中很常见，而MIC升高则取决于GyrA突变的类型。ParC T57S替换本身似乎对细菌适应性影响不大。质粒介导的喹诺酮耐药（PMQR）基因的存在代表了在无靶位点突变情况下耐药性产生的一条途径。观察到质粒介导的喹诺酮耐药（PMQR）基因位置从质粒转移到染色体，导致环丙沙星敏感性降低；这也与适应性增加和稳定的耐药表型相关。AcrAB - TolC的过表达在敏感性略有降低的分离株中起重要作用，其表达上调更多是由MarA而非RamA引起。本研究增进了我们对食物链中几种耐药机制在氟喹诺酮耐药性产生中相对重要性的理解。
