Genomic and Transcriptomic Analysis of Colistin-Susceptible and Colistin-Resistant Isolates Identify Two-Component System EvgS/EvgA Associated with Colistin Resistance in Escherichia coli

Abstract

Purpose

Colistin is one of the last-resort antimicrobial agents that combat the increasing threat of multi-drug resistant (MDR) gram-negative bacteria. Based on the known mechanism of colistin resistance which contributes to chromosomal mutations involved in the synthesis and modification of lipopolysaccharide (LPS), we explored the regulatory genes mediate colistin resistance, by whole genome sequencing and transcriptome analysis.

Materials and Methods

In this study, a colistin-resistant (Col^r) strain Escherichia coli ATCC 25922-R was generated from colistin-sensible (Col^s) strain E. coli ATCC 25922 by colistin induction. We compared the genome and transcriptome sequencing result from Col^s and Col^r strain. MALDI-TOF mass spectrometry was used to detect LPS.

Results

Genomic analysis and complementation experiment demonstrated the PmrB amino acid substitution in ATCC 25922-R (L14R) conferred the colistin resistance phenotype. Results of RNA sequencing (RNA-Seq) and comparative transcriptome analysis indicated that the two-component system EvgS/EvgA is highly involved in the global regulation of colistin resistance.

Conclusion

This study demonstrated that PmrB L14R amino acid substitution resulted in colistin resistance, and two-component system EvgS/EvgA might participate in colistin resistance in E. coli.

Keywords:

• colistin resistance
• Escherichia coli
• PmrAB
• EvgS/EvgA

Acknowledgment

We thank Hao Fu, for the technical support and quality control.

Disclosure

The authors report no conflicts of interest in this work.