OqxAB-Positive IncHI2 Plasmid pHXY0908 Increase Salmonella enterica Serotype Typhimurium Strains Tolerance to Ciprofloxacin.

Xinlei Lian,Xiran Wang,Xiaoping Liao,Jian Sun,Yahong Liu,Liangxing Fang,Xiao Liu,Jing Xia

doi:10.3389/fcimb.2019.00242

Xinlei Lian, Xiran Wang + Show 6 more

Open Access

https://doi.org/10.3389/fcimb.2019.00242

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Abstract

Salmonella enterica serotype Typhimurium is a major global food-borne pathogen and causes life-threatening infections. Although the resistance mechanisms to fluoroquinolones in S. Typhimurium had been well-defined, tolerance to fluoroquinolones and the associated mechanism for this are obscure. In the current work, we investigated an oqxAB-positive plasmid pHXY0908 and analyzed its role in S. Typhimurium tolerance to ciprofloxacin using time-kill, transcriptome sequencing and real-time PCR. S. Typhimurium ATCC14028 could survive under lethal concentrations of ciprofloxacin after acquiring plasmid pHXY0908. Transcriptome sequence analysis showed the chromosomal genes were systematically regulated after acquiring this plasmid suggesting an interaction between chromosome and plasmid. Additionally, the chromosomal efflux pump genes acrB, acrA, tolC, and yceE were up-regulated after acquiring plasmid pHXY0908 suggesting that these efflux pumps may contribute to the survival of ATCC14028 exposed to the lethal concentrations of ciprofloxacin. In conclusion, this is the first known report demonstrating that an IncHI2 type plasmid harboring oqxAB could assist S. Typhimurium survival under lethal concentrations of ciprofloxacin.

Highlights

Salmonella enterica Typhimurium is a major global food-borne pathogen, causing a wide spectrum of human and animal diseases including acute gastroenteritis, bacteremia, and extra intestinally localized infections involving many organs (Coburn et al, 2007)
Time-kill curve assays indicated a survival advantages at 1×, 2×, and 4× ciprofloxacin Minimum Inhibitory Concentration (MIC) levels for the plasmid bearing strain compared to the parental strain
The antibacterial activity of ciprofloxacin significantly decreased over the 3 h antibiotic exposure period against ATCC14028 strain harboring plasmid pHXY0908

Summary

Introduction

Salmonella enterica Typhimurium is a major global food-borne pathogen, causing a wide spectrum of human and animal diseases including acute gastroenteritis, bacteremia, and extra intestinally localized infections involving many organs (Coburn et al, 2007). The extensive use of antimicrobials in humans and animals has led to an increase in multi-drug resistance among numerous bacterial strains. Due to increasing resistance to the conventional antimicrobial agents such as ampicillin, chloramphenicol, and trimethoprim/sulfonamides, fluoroquinolones such as ciprofloxacin for the treatment of severe invasive salmonellosis has become more common (Hohmann, 2011). The use of fluoroquinolones has led to a rapid increase in reduced susceptibility of S. Typhimurium with reduced ciprofloxacin susceptibility has become common in China (Li et al, 2013a; Wong and Chen, 2013)

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