Analysis of Efflux Pump Contributions and Plasmid-Mediated Genetic Determinants in Ciprofloxacin-Resistant .

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.