Zhou Xiujuan, Yi Shanrong, Kuang Dai, Shi Chunlei, Qu Chunbo
College of Public Health, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.
School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Pathogens. 2024 Dec 20;13(12):1126. doi: 10.3390/pathogens13121126.
This study aimed to explore the interactions among genetic determinants influencing ciprofloxacin resistance in . Treatment with PAβN, an efflux pump inhibitor, resulted in a 4-32-fold reduction in the minimum inhibitory concentration (MIC) across all 18 ciprofloxacin-resistant isolates. Notably, isolates without point mutations reverted from resistance to sensitivity. The efflux pump played a crucial role in resistance development, particularly in serovar Enteritidis, where PAβN treatment caused a more significant MIC reduction (16-32-fold) in five strains carrying the GyrA (Asp87Tyr) mutation, which initially exhibited high MICs (8 μg/mL). Several resistance genes were identified on transferable plasmids: and were associated with IncF plasmids in Enteritidis, IncA/C plasmids in Typhimurium, and IncHI2 plasmids in Virchow. Additionally, and/or were carried by IncA/C plasmids in Thompson. Whole-genome sequencing revealed the presence of an module integrated into the chromosomal DNA of Derby. Although the MICs of ciprofloxacin in transconjugants and transformants remained low (1-4 μg/mL), they exceeded the clinical breakpoint for susceptibility. These findings highlight the synergistic impact of efflux pumps and plasmid-mediated resistance mechanisms, contributing to the increasing prevalence of ciprofloxacin resistance and posing a significant threat to food safety.
本研究旨在探讨影响环丙沙星耐药性的遗传决定因素之间的相互作用。用外排泵抑制剂PAβN处理后，所有18株环丙沙星耐药菌株的最低抑菌浓度（MIC）降低了4至32倍。值得注意的是，无点突变的菌株从耐药转变为敏感。外排泵在耐药性发展中起关键作用，特别是在肠炎血清型中，在携带GyrA（Asp87Tyr）突变的五株最初MIC较高（8μg/mL）的菌株中，PAβN处理导致MIC显著降低（16至32倍）。在可转移质粒上鉴定出几个耐药基因：在肠炎沙门氏菌中， 和 与IncF质粒相关，在鼠伤寒沙门氏菌中与IncA/C质粒相关，在维尔乔沙门氏菌中与IncHI2质粒相关。此外，在汤普森沙门氏菌中， 和/或 由IncA/C质粒携带。全基因组测序显示，德尔比沙门氏菌的染色体DNA中存在一个 模块。尽管转接合子和转化子中环丙沙星的MIC仍然较低（1至4μg/mL），但它们超过了临床敏感断点。这些发现突出了外排泵和质粒介导的耐药机制的协同影响，导致环丙沙星耐药性的日益普遍，并对食品安全构成重大威胁。
