Wang Jing, Guo Ze-Wen, Zhi Chan-Ping, Yang Tong, Zhao Jing-Jing, Chen Xiao-Jie, Zeng Li, Lv Lu-Chao, Zeng Zhen-Ling, Liu Jian-Hua
J Antimicrob Chemother. 2017 May 1;72(5):1293-1302. doi: 10.1093/jac/dkw576.
To investigate the impact of plasmid-borne oqxAB genes on the development of fluoroquinolone resistance, mutations and bacterial fitness in Escherichia coli .
MICs and mutation prevention concentrations were compared among E. coli strain TOP10 and two corresponding transformants harbouring the OqxAB-encoding plasmids. Mutants were selected by serial passages with the 0.5-fold MIC of ciprofloxacin, and were randomly selected to determine mutations. Bacterial fitness was evaluated by competition assays in vitro and in vivo .
The oqxAB -carrying plasmids contributed to a 4-8-fold increase in the ciprofloxacin MIC and increased the ciprofloxacin mutation prevention concentration by 8-16-fold. The MIC of ciprofloxacin for the two transformants increased faster than that of E. coli TOP10 by serial passaging. Novel mutations in gyrB (A468P or F458V) were first observed. Mutations in gyrA were distributed at codons 87 and 83 in the two transformants, whereas mutation A119E in gyrA dominated in the TOP10 mutants. Although the two oqxAB -bearing plasmids caused a decrease in fitness in vitro , their fitness increased when combined with more than one chromosomal mutation, and clear biological benefits were observed in vivo . The mutations in gyrB were associated with a fitness cost, which could be compensated for by additional mutations. The novel mutation gyrA ΔS83 significantly reduced biological fitness both in vitro and in vivo , and was thus quickly replaced by more beneficial mutations in the population.
The possession of plasmid-borne oqxAB may facilitate the evolution of fluoroquinolone resistance, and the fitness cost of OqxAB-encoding plasmids could be compensated by additional chromosomal mutations.
研究携带质粒的oqxAB基因对大肠杆菌氟喹诺酮耐药性发展、突变及细菌适应性的影响。
比较大肠杆菌TOP10菌株及两个携带编码OqxAB质粒的相应转化子的最低抑菌浓度（MIC）和突变预防浓度。通过用环丙沙星0.5倍MIC进行连续传代筛选突变体，并随机选择突变体确定突变情况。通过体外和体内竞争试验评估细菌适应性。
携带oqxAB的质粒使环丙沙星MIC增加4至8倍，并使环丙沙星突变预防浓度增加8至16倍。通过连续传代，两个转化子的环丙沙星MIC比大肠杆菌TOP10增加得更快。首次观察到gyrB基因的新突变（A468P或F458V）。gyrA基因的突变在两个转化子中分布于密码子87和83处，而在TOP10突变体中gyrA基因的A119E突变占主导。虽然两个携带oqxAB的质粒在体外导致适应性下降，但当与多个染色体突变结合时其适应性增加，并且在体内观察到明显的生物学益处。gyrB基因的突变与适应性代价相关，可通过额外的突变得到补偿。新突变gyrA ΔS83在体外和体内均显著降低生物学适应性，因此在群体中很快被更有益的突变所取代。
携带质粒的oqxAB可能促进氟喹诺酮耐药性的演变，并且编码OqxAB质粒的适应性代价可通过额外的染色体突变得到补偿。
