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. 2021 May 6:12:663731.
doi: 10.3389/fmicb.2021.663731. eCollection 2021.

Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp

Man-Xia Chang  1   2 , Jin-Fei Zhang  1 , Yin-Huan Sun  1 , Rong-Sheng Li  1 , Xiao-Ling Lin  1 , Ling Yang  1 , Mark A Webber  3   4 , Hong-Xia Jiang  1   2
Affiliations

Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp

Man-Xia Chang et al. Front Microbiol. .

Abstract

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.

Keywords: AcrAB efflux pump; PMQR; QRDR; Salmonella; circular intermediate; fluoroquinolone resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Ciprofloxacin MIC distributions in 176 Salmonella strains used in this study.
FIGURE 2
FIGURE 2
Formation of a circular intermediate by oqxABR operon. (A) Comparison between genetic structure of transposon Tn6010 located in pOLA52 (accession no. NC_010378) and the oqxABR operon positive strains. (B) The circular form of Tn6010 and the approximate locations of the reverse primers oqx-IF and oqx-IR (line arrows). (C) Gel electrophoresis of PCR amplicons corresponding to the circular intermediate of Tn6010, detectable in oqxABR-positive strains using the reverse primers oqx-IF and oqx-IR. Primers are listed in Supplementary Table 1. NC, Negative Control.
FIGURE 3
FIGURE 3
In vitro bacterial competition assays. Competition coefficient values were obtained from each independent experiment as indicated. Broken horizontal line, competition coefficient of 1; mean values, short continuous horizontal lines. –, not detected; C+, chromosomally located; P+, plasmid located.
FIGURE 4
FIGURE 4
Quinolone resistance genes associated with different ciprofloxacin MICs amongst isolates.
See this image and copyright information in PMC

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