Molecular mechanism of plasmid-encoded blaKPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli

BAI Shuancheng; YANG Lan; LUO Xiang; HUANG Liya; WANG Yuxin; WANG Rong; LIAO Fengting; LIAO Xiaoping

doi:10.7671/j.issn.1001-411X.202411006

Journal of South China Agricultural University > 2025 > 46(3): 326-335. > DOI: 10.7671/j.issn.1001-411X.202411006

BAI Shuancheng, YANG Lan, LUO Xiang, et al. Molecular mechanism of plasmid-encoded bla_KPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli[J]. Journal of South China Agricultural University, 2025, 46(3): 326-335. DOI: 10.7671/j.issn.1001-411X.202411006

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Molecular mechanism of plasmid-encoded bla_KPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli

1.
Smart Agriculture College, Yulin Normal College, Yulin 537000, China
2.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

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Received Date: November 04, 2024
Available Online: March 13, 2025
Published Date: March 26, 2025

Graphical Abstract

Abstract

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 bla_KPC-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 bla_KPC-2 gene encoded on the plasmid mediating low-level resistance to carbapenems in E. coli is related to the regulation of bla_KPC-2 gene by ompR.
- Escherichia coli,
- OmpR gene,
- Klebsiella pneumoniae carbapenemase-2,
- Carbapenems,
- Drug resistance,
- Molecular mechanism

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References (29)

References

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Molecular mechanism of plasmid-encoded blaKPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli

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Molecular mechanism of plasmid-encoded bla_KPC-2 gene mediating low-level resistance to carbapenems in Escherichia coli