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

• Published in: Pathogens (Basel) Vol. 13; no. 12; p. 1126
• Main Authors: Zhou, Xiujuan, Yi, Shanrong, Kuang, Dai, Shi, Chunlei, Qu, Chunbo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2024
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Ciprofloxacin; Ciprofloxacin - pharmacology; DNA sequencing; Drug Resistance, Bacterial - genetics; E coli; Efflux; Food; Food contamination & poisoning; Food products; Food safety; Gene mutations; Gene sequencing; Genes; Genetic analysis; Genetic aspects; Genomes; Genomics; Humans; Impact resistance; Membrane Transport Proteins - genetics; Microbial Sensitivity Tests; Minimum inhibitory concentration; Mutation; Nucleotide sequencing; plasmid fusion; plasmid-mediated quinolone resistance; Plasmids; Plasmids - genetics; Point mutation; Quality control; Safety and security measures; Salmonella; Salmonella - drug effects; Salmonella - genetics; Salmonella Infections - drug therapy; Salmonella Infections - genetics; Salmonella Infections - microbiology; Whole genome sequencing; China; Beijing China; United States > US; Germany; Salmonella; plasmid fusion; plasmid-mediated quinolone resistance; ciprofloxacin
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens13121126

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.