Evolution of carbapenem resistance in klebsiella pneumoniae and escherichia coli carrying blaNDM−1 gene: imipenem exposure results in sustained resistance memory of strains in vitro

Annals of Clinical Microbiology and Antimicrobials

Research

Feixiang Yang¹  Hua Zhang¹  Lingling Wu¹  Lixue Meng²  Longhua Sha²  Qiong Zhao²  Chunfang Yu²  Zhaomeng Wu²  Zhixiong Jin³  Jingdan Yu⁴ 

[1] Department of Clinical Laboratory, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, 442008, Hubei, Shiyan, China;Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, 442000, Hubei, Shiyan, China;Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, 442000, Hubei, Shiyan, China;Department of Clinical Laboratory, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, 442008, Hubei, Shiyan, China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, 442000, Hubei, Shiyan, China;Laboratory Medicine, Wuhan Asia General Hospital, 430050, Hubei, Wuhan, China;

关键词: Klebsiella pneumoniae;    Escherichia coli;    β;    bla;    Imipenem;    Drug resistance;   

DOI  :  10.1186/s12941-023-00598-8

 received in 2022-05-05, accepted in 2023-05-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAntibiotics exert an outstanding selective pressure on bacteria, forcing their chromosomal gene mutations and drug resistance genes to spread. The objective of this study is to evaluate the expression of the New Delhi Metallo-β-Lactamase-1 gene (blaNDM−1) in the clinical isolate (Klebsiella pneumoniae TH-P12158), transformant strains Escherichia coli BL21 (DE3)-blaNDM−1, and Escherichia coli DH5α- blaNDM−1 when exposed to imipenem.Methodsβ-Lactamase genes (blaSHV, blaTEM−1, blaCTX−M−9, blaIMP, blaNDM−1, blaKPC, blaOXA, blaGES, and blaDHA) from randomly selected carbapenems-sensitive K.pneumoniae (n = 20) and E.coli (n = 20) strains were amplified by PCR. The recombinant plasmid of pET-28a harboring blaNDM−1 was transformed into E.coli BL21 (DE3) and E.coli DH5α by electroporation. The resistance phenotype and higher blaNDM−1 expression in K.pneumoniae TH-P12158, transformant E.coli BL21 (DE3)-blaNDM−1, and E.coli DH5α-blaNDM−1 were observed when exposed to imipenem with grade increasing, decreasing, and canceling doses, respectively.ResultsAfter being exposed to different doses of imipenem, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of antimicrobial drugs and blaNDM−1 expression of strains increased, which was positively correlated with doses of imipenem. On the contrary, with the decrease or cancellation of imipenem doses, the blaNDM−1 expression was deteriorated, while the MIC and MBC values remained relatively stable. These results demonstrated that low doses of imipenem (˂MIC) could press blaNDM−1 positive strains producing stable drug resistance memory and altered blaNDM−1 expression.ConclusionsLow doses of imipenem could press blaNDM−1 positive strains producing sustained resistance memory and altered blaNDM−1 expression. In particular, the positive correlation between the resistance genes expression and antibiotics exposure shows promising guiding significance for clinical medication.

【 授权许可】

CC BY   
© The Author(s) 2023

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