Abstract
The aim of this study was to investigate the difference in resistance mechanisms and fitness of Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE) mutants selected during the evolution of resistance under exposure to increasing ciprofloxacin concentrations in vitro. Mutations in quinolone target genes were screened by PCR. Phenotypic characterization included susceptibility testing by the broth dilution method, investigation of efflux activity and growth rate, and determination of the invasion of human intestinal epithelium cells in vitro. The two Salmonella serotypes exhibited differences in target gene mutations and efflux pump gene expression during the development of resistance. In the parental strains, ST had a competitive advantage over SE. During the development of resistance, initially, the SE strain was more competitive. However, once ciprofloxacin resistance was acquired, ST once again became the more competitive strain. In the absence of bile salts or at 0.1% bile, the growth rate of SE was initially greater than that of ST, but once ciprofloxacin resistance was acquired, ST had higher growth rates. ST strains showed decreased invasion of epithelial cells in 0.1% bile. These data indicate that ciprofloxacin-resistant ST strains are more competitive than ciprofloxacin-resistant SE strains.
Highlights
Salmonella exhibit high morbidity and mortality, and are important pathogens worldwide
When the ciprofloxacin concentration increased to 2 mg/L, mutant Salmonella Typhimurium (ST)-M3 acquired high-level resistance to ciprofloxacin; an additional mutation in ParC (G78D) was detected, but this was subsequently restored with further increases in ciprofloxacin concentration, leading to a fourfold decrease in the ciprofloxacin MIC in the subsequent mutants (ST-M4, ST-M5, ST-M6)
To determine the role of mutation ParC G78D in ciprofloxacin resistance, we examined the effect of complementation with the parental strain parC gene by determining antibiotic susceptibilities
Summary
Salmonella exhibit high morbidity and mortality, and are important pathogens worldwide. Recent reports have shown high isolation rates of FQ-resistant Salmonella strains from poultry samples[5]. FQ-resistance in Gram-negative bacteria is primarily due to the acquisition of mutations located in chromosomal genes encoding quinolone targets and, to a lesser extent, the overexpression of efflux pumps such as AcrAB-TolC or changes in outer membrane proteins (e.g., OmpF and OmpC)[6, 7]. Amino acid substitutions at positions 83 and 87 of GyrA are the most frequently reported mutations in FQ-resistant isolates[8, 9]. Mediated FQ resistance mutations have been reported to be associated with decreased fitness[10]. The acrAB and tolC genes, which encode the major multidrug AcrAB-TolC efflux system, required for the bile resistance of Salmonella, are transcriptionally activated by bile[16]
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