Zhang Wen-Hui, Zhang Chuan-Zhen, Liu Zhi-Jie, Gu Xi-Xi, Li Wan, Yang Ling, Liu Ya-Hong, Zeng Zhen-Ling, Jiang Hong-Xia
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University (SCAU) , Guangzhou, China .
Microb Drug Resist. 2017 Sep;23(6):687-694. doi: 10.1089/mdr.2016.0119. Epub 2017 Jan 13.
Difference in the development of resistance may be associated with the epidemiological spread and drug resistance of different Salmonella enterica serovar strains. In the present study, three susceptible S. enterica serovars, Typhimurium (ST), Enteritidis (SE), and Indiana (SI) strains, were subjected to stepwise selection with increasing ciprofloxacin concentrations. The results indicated that the mutation frequencies of the SI group were 10-10 higher and developed resistance to ciprofloxacin more rapidly compared with the ST and SE groups. Ciprofloxacin accumulation in the SI strain was also higher than the other two strains in the presence of an efflux pump inhibitor. The development of ciprofloxacin resistance was quite different among the three serovar strains. In SI, increasing AcrAB-TolC efflux pump expression and single or double mutations in gyrA with or without a single parC mutation (T57S) were found in the development of ciprofloxacin resistance. In SE, an increase in the AcrAB-TolC efflux pump regulatory gene ramA gradually decreased as resistant bacteria developed; then resistance resulted from gyrA D87G and gyrB E466D mutations and/or in other active efflux pumps besides AcrAB-TolC. For ST, ramA expression increased rapidly along with gyrA D87 N and/or gyrB S464F mutations. In conclusion, persistent use of ciprofloxacin may aggravate the resistance of different S. enterica serovars and prudent use of the fluoroquinolones is needed. The quicker resistance and higher mutation frequency of the SI isolates present a potential public health threat.
耐药性发展的差异可能与不同肠炎沙门氏菌血清型菌株的流行病学传播和耐药性有关。在本研究中，三种敏感的肠炎沙门氏菌血清型，鼠伤寒沙门氏菌（ST）、肠炎沙门氏菌（SE）和印第安纳沙门氏菌（SI）菌株，用逐渐增加的环丙沙星浓度进行逐步筛选。结果表明，与ST和SE组相比，SI组的突变频率高10 - 10倍，对环丙沙星产生耐药性的速度更快。在存在外排泵抑制剂的情况下，SI菌株中环丙沙星的蓄积也高于其他两种菌株。三种血清型菌株中环丙沙星耐药性的发展有很大差异。在SI中，发现环丙沙星耐药性发展过程中AcrAB - TolC外排泵表达增加以及gyrA发生单突变或双突变，有或无parC单突变（T57S）。在SE中，随着耐药菌的出现，AcrAB - TolC外排泵调节基因ramA的增加逐渐减少；然后耐药性由gyrA D87G和gyrB E466D突变和/或除AcrAB - TolC之外的其他活性外排泵导致。对于ST，ramA表达随着gyrA D87N和/或gyrB S464F突变迅速增加。总之，持续使用环丙沙星可能会加重不同肠炎沙门氏菌血清型的耐药性，需要谨慎使用氟喹诺酮类药物。SI分离株更快的耐药性和更高的突变频率对公共卫生构成潜在威胁。
