Gu Yufeng, Wang Shuge, Huang Lulu, Sa Wei, Li Jun, Huang Junhong, Dai Menghong, Cheng Guyue
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China.
Antibiotics (Basel). 2020 Nov 10;9(11):791. doi: 10.3390/antibiotics9110791.
Quinoxaline1,4-di--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 () under the pressure of sub-inhibitory concentration (sub-MIC) of olaquindox (OLA), a representative QdNOs drug. In vitro challenge of 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 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 , , , , , and 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.
喹喔啉 1,4-二氧化物（QdNOs）是一类重要的兽用抗菌药物，其耐药机制尚未得到明确解释。本研究调查了在代表性 QdNOs 药物喹乙醇（OLA）亚抑菌浓度（亚 MIC）压力下，（某细菌名称未给出）耐药性产生的分子机制。用 1/100×MIC 至 1/2×MIC 的 OLA 对（某细菌名称未给出）进行体外挑战试验表明，该细菌产生耐药所需时间更长，且只能达到低至中等水平的耐药性，同时形成较弱的生物膜。由 OLA 亚 MIC 诱导产生的耐药（某细菌名称未给出）的转录组和基因组图谱显示，参与三羧酸循环、氧化还原过程、生物膜形成和外排泵的基因上调，而参与 DNA 修复和外膜孔蛋白的基因下调。亚 MIC OLA 处理的细菌突变率显著增加，突变基因主要参与氧化还原过程、DNA 修复和复制。在（某细菌名称未给出）的（具体基因名称未给出）、（具体基因名称未给出）、（具体基因名称未给出）、（具体基因名称未给出）、（具体基因名称未给出）和（具体基因名称未给出）基因中发现了单核苷酸多态性（SNPs），这些基因在转录组和基因组图谱中均有覆盖。本研究为 QdNOs 的耐药机制提供了新的见解，并增加了关于亚 MIC 浓度抗菌药物压力下细菌耐药性产生的现有数据。
