华南农业大学学报2025，Vol.46Issue(3)：326-335,10.DOI:10.7671/j.issn.1001-411X.202411006
大肠埃希菌质粒编码的blaKPC-2 基因介导碳青霉烯类药物低水平耐药的分子机制
Molecular mechanism of plasmid-encoded blaKPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli
摘要
Abstract
[Objective]To elucidate the molecular mechanism by which the carbapenemase-encoding plasmid p21QH43K-KPC is transferred from Klebsiella pneumoniae to Escherichia coli,and mediates low-level resistance to carbapenem drugs in E.coli.[Method]The construction of EZ-Tn5 transposon mutation library,CRISPR-Cas9-mediated gene knockout,transcriptome sequencing and whole genome sequencing(WGS)were used to determine the regulatory mechanism of low-level resistance to meropenem mediated by the blaKPC-2 gene in E.coli.[Result]A transposon mutant EC600/p21QH43K-KPC-130 with enhanced meropenem resistance(MIC=8.000 mg/L)was obtained by constructing the EZ-Tn5 transposon mutation library of the EC600/p21QH43K-KPC conjugon.WGS and Mauve analysis revealed that the transposon had inserted into one chromosomal gene ompR,and two point mutation genes of iron and ltrA were found.However,through gene knockout,only ompR deletion mutants exhibited reduced sensitivity to carbapenem that could be restored by gene complementation.[Conclusion]The molecular mechanism of the blaKPC-2 gene encoded on the plasmid mediating low-level resistance to carbapenems in E.coli is related to the regulation of blaKPC-2 gene by ompR.关键词
大肠埃希菌/OmpR基因/肺炎克雷伯菌碳青霉烯酶-2/碳青霉烯类药物/耐药性/分子机制Key words
Escherichia coli/OmpR gene/Klebsiella pneumoniae carbapenemase-2/Carbapenems/Drug resistance/Molecular mechanism分类
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白栓成,杨澜,罗湘,黄丽雅,王雨欣,王熔,廖凤婷,廖晓萍..大肠埃希菌质粒编码的blaKPC-2 基因介导碳青霉烯类药物低水平耐药的分子机制[J].华南农业大学学报,2025,46(3):326-335,10.基金项目
玉林师范学院高层次人才科研启动基金(G2024ZK13) （G2024ZK13）
国家重点研发计划(2023YFD1800100) （2023YFD1800100）
广东省珠江人才计划本地创新研究团队项目(2019BT02N054) （2019BT02N054）
