Journal
FRONTIERS IN MICROBIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2021.663731
Keywords
fluoroquinolone resistance; AcrAB efflux pump; QRDR; PMQR; circular intermediate; Salmonella
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Funding
- National Natural Science Foundation of China [31772792]
- National Key Research Program of China [2016YFD0501300]
- Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Microbes in the Food Chain [BB/R012504/1, BBS/E/F/000PR10349]
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The study analyzed 176 Salmonella isolates from animals with different ciprofloxacin MICs and found that the ParC T57S substitution was common in strains with low ciprofloxacin MICs, while increased MICs depended on the type of GyrA mutation. The presence of PMQR genes provided a route for resistance development in the absence of target-site mutations, and the transfer of plasmid-mediated quinolone resistance genes from plasmids to chromosomes resulted in decreased ciprofloxacin susceptibility and increased fitness. Additionally, overexpression of AcrAB-TolC played a significant role in isolates with slight decreases in susceptibility, with expression being upregulated by MarA more frequently than by RamA.
Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.
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