Resistance characterization and transcriptomic analysis of imipenem-induced drug resistance in Escherichia coli

PeerJ. 2024 Nov 29:12:e18572. doi: 10.7717/peerj.18572. eCollection 2024.

Abstract

Background: Bacteria can develop resistance to various antibiotics under selective pressure, leading to multifaceted changes in resistance mechanisms. Transcriptomic sequencing allows for the observation of transcriptional level alterations in cells under antibiotic stress. Understanding the bacterial response to such stress is essential for deciphering their strategy against drug-resistant antibiotics and identifying potential targets for antibiotic development.

Methods: This study using wild-type (WT) Escherichia coli (E. coli) discovered that continuous in vitro induction screening for imipenem-resistant strains resulted in bacteria with enhanced biofilm-forming ability and mutations in antibiotic target sites. Transcriptomic sequencing of the resistant bacteria revealed significant changes in carbon and amino acid metabolism, nutrient assimilation, substance transport, nucleotide metabolism, protein biosynthesis, and cell wall biosynthesis. The up-regulated drug efflux genes were disrupted using gene knockout technology. Drug sensitivity tests indicated that drug efflux has a minimal effect on imipenem resistance.

Results: This suggests a strategy for E. coli drug resistance involving the reduction of unnecessary substance synthesis and metabolism, coupled with an increase in activities that aid in resisting foreign threats.

Keywords: Biofilm; Efflux pumps; Escherichia coli; Imipenem; Transcriptomics.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Biofilms / drug effects
  • Drug Resistance, Bacterial* / drug effects
  • Drug Resistance, Bacterial* / genetics
  • Escherichia coli* / drug effects
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Bacterial / drug effects
  • Imipenem* / pharmacology
  • Microbial Sensitivity Tests
  • Transcriptome / drug effects

Substances

  • Imipenem
  • Anti-Bacterial Agents

Grants and funding

This research was funded by the Key Research and Development Project of Heilongjiang Province of China, grant number GZ20210101; the Cultivation Project of Heilongjiang Bayi Agricultural University, grant number XDB-2016-22; the Postdoctoral Scientific Research Start-up Fund of Heilongjiang, grant number LBH-Q21158. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.