Abstract
The evolution of resistance in Salmonella to fluoroquinolones (FQs) under a broad range of sub-inhibitory concentrations (sub-MICs) has not been systematically studied. This study investigated the mechanism of resistance development in Salmonella enterica serovar Enteritidis (S. Enteritidis) under sub-MICs of 1/128×MIC to 1/2×MIC of enrofloxacin (ENR), a widely used veterinary FQ. It was shown that the resistance rate and resistance level of S. Enteritidis varied with the increase in ENR concentration and duration of selection. qRT-PCR results demonstrated that the expression of outer membrane porin (OMP) genes, ompC, ompD and ompF, were down-regulated first to rapidly adapt and develop the resistance of 4×MIC, and as the resistance level increased (≥8×MIC), the up-regulated expression of efflux pump genes, acrB, emrB amd mdfA, along with mutations in quinolone resistance-determining region (QRDR) gradually played a decisive role. Cytohubba analysis based on transcriptomic profiles demonstrated that purB, purC, purD, purF, purH, purK, purL, purM, purN and purT were the hub genes for the FQs resistance. The ‘de novo’ IMP biosynthetic process, purine ribonucleoside monophosphate biosynthetic process and purine ribonucleotide biosynthetic process were the top three biological processes screened by MCODE. This study first described the dynamics of FQ resistance evolution in Salmonella under a long-term selection of sub-MICs of ENR in vitro. In addition, this work offers greater insight into the transcriptome changes of S. Enteritidis under the selection of ENR and provides a framework for FQs resistance of Salmonella for further studies.
Highlights
The selection acted more efficiently for a higher ENR concentration to select for resistance
It was found that clinical Salmonella isolates evolved a high level of ciprofloxacin (CIP) resistance that was accompanied by additional mutations in GyrA and ParE [26]
Our results revealed that AcrEF and MdtK efflux may have little contribution to ENR resistance at early stage, while AcrAB, EmrAB and MdfABC may play an important role in ENR resistance, since the expression level of acrB, emrB, mdfA was increased with increased level of FQs resistance and acrB gene was significantly increased, while the expression of the acrF and mdtK gene down-regulated as the susceptibility reduced (Figure 2 and Table 4)
Summary
Enteritidis), a zoonotic foodborne pathogen, has been widely recognized as one of the most common causes of gastroenteritis in humans [1]. According to the report of World Health Organization, Salmonella enterica serovar Typhimurium Enteritidis are the most frequently isolated Salmonella serotypes from countries involved in the Global Foodborne Infections Network [2]. Fluoroquinolones (FQs) have been broadly applied in clinical practice for treating Salmonellosis in both humans and animals [3,4]. The emergence of resistance to FQs has become a critical problem in clinical treatment of Salmonellosis [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
