Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Int J Mol Sci. 2021 Sep 17;22(18):10036. doi: 10.3390/ijms221810036.
is a pathogen that infects pigs and poses a serious threat to the pig industry. The emergence of quinolone-resistant strains of further limits the choice of treatment. However, the mechanisms behind quinolone resistance in remain unclear. The genomes of a ciprofloxacin-resistant strain, SC1810 and its isogenic drug-sensitive counterpart were sequenced and analyzed using various bioinformatics tools, revealing 559 differentially expressed genes. The biological membrane, plasmid-mediated quinolone resistance genes and quinolone resistance-determining region were detected. Upregulated expression of efflux pump genes led to ciprofloxacin resistance. The expression of two porins, OmpP2B and LamB, was significantly downregulated in the mutant. Three nonsynonymous mutations in the mutant strain disrupted the water-metal ion bridge, subsequently reducing the affinity of the quinolone-enzyme complex for metal ions and leading to cross-resistance to multiple quinolones. The mechanism of quinolone resistance in may involve inhibition of expression of the outer membrane protein genes and to decrease drug influx, overexpression of AcrB in the efflux pump to enhance its drug-pumping ability, and mutation in the quinolone resistance-determining region to weaken the binding of the remaining drugs. These findings will provide new potential targets for treatment.
是一种感染猪的病原体，对养猪业构成严重威胁。喹诺酮类耐药菌株的出现进一步限制了治疗选择。然而， 中喹诺酮类耐药的机制仍不清楚。使用各种生物信息学工具对环丙沙星耐药株 SC1810 及其同源性药物敏感对照株的基因组进行了测序和分析，共发现 559 个差异表达基因。检测到生物膜、质粒介导的喹诺酮类耐药基因和喹诺酮类耐药决定区。外排泵基因的上调表达导致环丙沙星耐药。突变株中两种孔蛋白基因 OmpP2B 和 LamB 的表达显著下调。突变株中三个非同义突变破坏了水-金属离子桥，随后降低了喹诺酮-酶复合物对金属离子的亲和力，导致对多种喹诺酮类药物的交叉耐药。 中喹诺酮类耐药的机制可能涉及抑制外膜蛋白基因 和 的表达，以减少药物内流，增强外排泵 AcrB 的表达以增强其药物泵出能力，以及喹诺酮耐药决定区的突变以削弱剩余药物的结合能力。这些发现将为治疗提供新的潜在靶点。
