Development of Resistance in Escherichia coli ATCC25922 under Exposure of Sub-Inhibitory Concentration of Olaquindox.

Yufeng Gu,Junhong Huang,Menghong Dai,Wei Sa,Guyue Cheng,Lulu Huang,Shuge Wang,Jun Li

doi:10.3390/antibiotics9110791

Yufeng Gu, Junhong Huang + Show 6 more

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https://doi.org/10.3390/antibiotics9110791

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Journal: Antibiotics	Publication Date: Nov 10, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Huazhong Agricultural University

Abstract

Quinoxaline1,4-di-N-oxides (QdNOs) are a class of important antibacterial drugs of veterinary use, of which the drug resistance mechanism has not yet been clearly explained. This study investigated the molecular mechanism of development of resistance in Escherichia coli (E. coli) under the pressure of sub-inhibitory concentration (sub-MIC) of olaquindox (OLA), a representative QdNOs drug. In vitro challenge of E. coli with 1/100× MIC to 1/2× MIC of OLA showed that the bacteria needed a longer time to develop resistance and could only achieve low to moderate levels of resistance as well as form weak biofilms. The transcriptomic and genomic profiles of the resistant E. coli induced by sub-MIC of OLA demonstrated that genes involved in tricarboxylic acid cycle, oxidation-reduction process, biofilm formation, and efflux pumps were up-regulated, while genes involved in DNA repair and outer membrane porin were down-regulated. Mutation rates were significantly increased in the sub-MIC OLA-treated bacteria and the mutated genes were mainly involved in the oxidation-reduction process, DNA repair, and replication. The SNPs were found in degQ, ks71A, vgrG, bigA, cusA, and DR76-4702 genes, which were covered in both transcriptomic and genomic profiles. This study provides new insights into the resistance mechanism of QdNOs and increases the current data pertaining to the development of bacterial resistance under the stress of antibacterials at sub-MIC concentrations.

Highlights

IntroductionResistant bacteria infection is one of the most pressing concerns of global societies, which has substantially contributed to the clinic and economic burden of the healthcare system [1].During the use of antibacterials, microorganisms are frequently exposed to drug concentrations below the minimal inhibitory concentration (MIC), which is called sub-inhibitory concentration (sub-MIC) [2].The origins of sub-MIC concentration of the antibacterial environment are versatile
In recent years, resistant bacteria infection is one of the most pressing concerns of global societies, which has substantially contributed to the clinic and economic burden of the healthcare system [1].During the use of antibacterials, microorganisms are frequently exposed to drug concentrations below the minimal inhibitory concentration (MIC), which is called sub-inhibitory concentration [2].The origins of sub-MIC concentration of the antibacterial environment are versatile
From the 200th generation, 1/2× MIC and 1/4× MIC OLA-induced bacteria appeared colonies on plates containing 2, 4, and 8 times MIC of OLA, and the highest resistance rate was above 3% in the 600th generation

Summary

Introduction

Resistant bacteria infection is one of the most pressing concerns of global societies, which has substantially contributed to the clinic and economic burden of the healthcare system [1].During the use of antibacterials, microorganisms are frequently exposed to drug concentrations below the minimal inhibitory concentration (MIC), which is called sub-inhibitory concentration (sub-MIC) [2].The origins of sub-MIC concentration of the antibacterial environment are versatile. Resistant bacteria infection is one of the most pressing concerns of global societies, which has substantially contributed to the clinic and economic burden of the healthcare system [1]. During the use of antibacterials, microorganisms are frequently exposed to drug concentrations below the minimal inhibitory concentration (MIC), which is called sub-inhibitory concentration (sub-MIC) [2]. The origins of sub-MIC concentration of the antibacterial environment are versatile. The concentration of natural antibacterials produced by bacteria and fungi in the environment is often lower than the MIC of pathogens [3]. Carcasses and excreta of animals that have used antibacterial drugs generate antibacterial gradients in the body and in the surrounding environment [4]. The poor therapeutic schedule of antibacterials treatment and preventive use of antibacterials, as well as Antibiotics 2020, 9, 791; doi:10.3390/antibiotics9110791 www.mdpi.com/journal/antibiotics

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