Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Gastroenterology, Gastroenterology Institute of Jiangxi Province, Nanchang, Jiangxi, China.
Gut Microbes. 2024 Jan-Dec;16(1):2379439. doi: 10.1080/19490976.2024.2379439. Epub 2024 Jul 25.
Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in . Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.
外排泵在抗生素耐药性的发展中起着至关重要的作用。本研究旨在探讨 中，外排泵基因表达与耐药基因突变之间的关系。选择了 26 株具有不同耐药特征的临床株进行进一步实验。诱导 7 株敏感株产生耐药性，并记录外排泵基因和点突变的表达。选择 4 株敏感株进行候选突变构建，并检测外排泵基因表达的变化。构建外排泵基因敲除株，并评估其对预防和逆转抗生素耐药基因突变的影响。结果表明，在多药耐药组中，外排泵基因 hefA 和 hefD 的表达明显高于其他组。在抗生素诱导耐药过程中，外排泵基因表达并未表现出稳定的增加或减少。在 23S rRNA 中 A2143G 或 A2142G 点突变的菌株中，hefA 基因的表达较低。gyrA 中 87K/91N、87N/91G、87K/91D 或 87N/91Y 以及 rdxA 中的 194insertA 突变株和野生型株相比，hefA 基因的表达较高。在抗生素诱导耐药过程中，与野生型株相比，外排泵基因 hefA 敲除株在 23S rRNA、gyrA 或 rdxA 基因中发生突变的时间较晚。外排泵基因敲除可以在一定程度上逆转某些菌株对克拉霉素或甲硝唑的表型耐药性，但对耐药基因突变无影响。本研究表明，不同的耐药基因突变可能对外排泵基因表达产生不同的影响。外排泵基因敲除可以在一定程度上延迟或预防抗生素耐药基因突变，并在某些菌株中逆转克拉霉素和甲硝唑的表型耐药性。
