Abstract

ABSTRACT Ciprofloxacin resistance in Salmonella has been increasingly reported due to the emergence and dissemination of multiple Plasmid-Mediated Quinolone Resistance (PMQR) determinants, which are mainly located in non-conjugative plasmids or chromosome. In this study, we aimed to depict the molecular mechanisms underlying the rare phenomenon of horizontal transfer of ciprofloxacin resistance phenotype in Salmonella by conjugation experiments, S1-PFGE and complete plasmid sequencing. Two types of non-conjugative plasmids, namely an IncX1 type carrying a qnrS1 gene, and an IncH1 plasmid carrying the oqxAB-qnrS gene, both ciprofloxacin resistance determinants in Salmonella, were recovered from two Salmonella strains. Importantly, these non-conjugative plasmids could be fused with a novel Incl1 type conjugative helper plasmid, which could target insertion sequence (IS) elements located in the non-conjugative, ciprofloxacin-resistance-encoding plasmid through replicative transcription, eventually forming a hybrid conjugative plasmid transmissible among members of Enterobacteriaceae. Since our data showed that such conjugative helper plasmids are commonly detectable among clinical Salmonella strains, particularly S. Typhimurium, fusion events leading to generation and enhanced dissemination of conjugative ciprofloxacin resistance-encoding plasmids in Salmonella are expected to result in a sharp increase in the incidence of resistance to fluoroquinolone, the key choice for treating life-threatening Salmonella infections, thereby posing a serious public health threat.

Highlights

  • Salmonella is a leading cause of food-borne illness worldwide [1]

  • Ciprofloxacin resistance mediated by conjugative plasmids in Salmonella In our previous study, a total of 157 non-repeated Salmonella isolates were recovered from 348 meat samples [16]

  • Bacterial resistance to fluoroquinolones such as ciprofloxacin is known to be mediated by target gene mutations

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Summary

Introduction

Salmonella is a leading cause of food-borne illness worldwide [1]. Intestinal salmonellosis is usually selflimiting and resolves within a week, while in patients at the extremes of age and those who are immunocompromise, it can cause systematic infections leading to death. A conjugative fusion plasmid that carried the blaCTX-M and PMQR genes, encoding resistance to both ceftriaxone and ciprofloxacin respectively, was reported This fusion plasmid was found to exist in a dynamic form in Salmonella in such a way that the strain contained both the fusion plasmid and two daughter plasmids [15]. We report the emergence of a type of broad-host range conjugative helper plasmid that could be fused with a non-conjugative plasmid carrying multiple PMQR genes, thereby transforming the latter into a conjugative, ciprofloxacin resistance-encoding plasmid. These data indicated that ciprofloxacin resistance in Salmonella mediated by many new mechanisms has evolved quickly and continuous monitoring is urgently needed

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