Analysis of Efflux Pump Contributions and Plasmid-Mediated Genetic Determinants in Ciprofloxacin-Resistant Salmonella
Xiujuan Zhou1,2, Shanrong Yi2, Dai Kuang2
1College of Public Health, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.
Abstract:
This study aimed to explore the interactions among genetic determinants influencing ciprofloxacin resistance in Salmonella. 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 Salmonella 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: oqxAB and aac(6')-Ib-cr were associated with IncF plasmids in S. Enteritidis, IncA/C plasmids in S. Typhimurium, and IncHI2 plasmids in S. Virchow. Additionally, qnrS1 and/or qepA were carried by IncA/C plasmids in S. Thompson. Whole-genome sequencing revealed the presence of an oqxAB module integrated into the chromosomal DNA of S. 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.
Insights
Efflux pumps and transferable plasmids significantly drive ciprofloxacin resistance in Salmonella. Inhibiting efflux pumps restored sensitivity in some strains, revealing key genetic interactions.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Ciprofloxacin resistance in Salmonella poses a significant threat to public health and food safety.
- Understanding the genetic mechanisms underlying resistance is crucial for developing effective control strategies.
Purpose of the Study:
- To investigate the interplay between genetic factors contributing to ciprofloxacin resistance in Salmonella.
- To evaluate the role of efflux pumps and plasmid-mediated genes in conferring resistance.
Main Methods:
- Treatment of resistant Salmonella isolates with PAβN (efflux pump inhibitor) to assess changes in minimum inhibitory concentration (MIC).
- Identification and characterization of resistance genes (e.g., oqxAB, aac(6')-Ib-cr, qnrS1, qepA) on transferable plasmids using whole-genome sequencing.
- Analysis of genetic mutations, including GyrA (Asp87Tyr), and their impact on resistance.
Main Results:
- PAβN treatment reduced ciprofloxacin MIC by 4-32 fold, restoring sensitivity in isolates lacking specific mutations.
- Efflux pumps were critical for resistance, especially in Salmonella Enteritidis, where PAβN caused a 16-32 fold MIC reduction in strains with GyrA mutations.
- Various resistance genes were found on transferable plasmids (IncF, IncA/C, IncHI2) across different Salmonella serovars.
- Chromosomal integration of oqxAB was observed in Salmonella Derby, with resulting MICs exceeding clinical susceptibility breakpoints.
Conclusions:
- Efflux pumps and plasmid-mediated genes act synergistically to promote ciprofloxacin resistance in Salmonella.
- These combined mechanisms contribute to the increasing prevalence of resistance, jeopardizing food safety.
- Targeting efflux pumps and understanding plasmid dynamics are essential for combating Salmonella resistance.
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