A novel incompatibility group X3 plasmid carrying blaNDM-1 encodes a small RNA that regulates host fucose metabolism and biofilm formation

RNA Biol. 2020 Dec;17(12):1767-1776. doi: 10.1080/15476286.2020.1780040. Epub 2020 Jun 28.

Abstract

The emergence of New Delhi metallo-beta-lactamase (NDM-1) has become a major health threat to clinical managements of gram-negative bacteria infections. A novel incompatibility group X3 plasmid (IncX3) pNDM-HN380 carrying blaNDM-1 has recently been found to epidemiologically link with multiple geographical areas in China. In this paper, we studied the metabolic responses of host bacteria E. coli J53 upon introduction of pNDM-HN380. A reduction of bacterial motility was observed in J53/pNDM-HN380. We profiled the RNA repertoires of the transconjugants and found a downregulation of genes involved in flagella and chemotaxis metabolic pathways at logarithmic (log) phase. We also identified a novel intragenic region (IGR) small RNA plas2. The plasmid-transcribed sRNA IGR plas2 was further characterized as a regulator of fucRwhich controls the fucose metabolism. By knockdown of IGR plas2 using an antisense decoy, we managed to inhibit the formation of bacterial biofilm of the host. Our study demonstrated a potential way of utilizing plasmid-transcribed sRNA against infectious bacteria.

Keywords: Drug resistance; IGR plas2; MDR; NDM1; RNA-seq; plasmid; sRNA; transcriptomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biofilms / growth & development*
  • Carbohydrate Metabolism / drug effects
  • Computational Biology / methods
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Fucose / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microbial Sensitivity Tests
  • Plasmids / genetics*
  • RNA, Bacterial*
  • Transcriptome
  • beta-Lactamases / genetics*

Substances

  • RNA, Bacterial
  • Fucose
  • beta-Lactamases
  • beta-lactamase NDM-1

Grants and funding

This work was supported by the Shenzhen Science and Technology Program [JCYJ20180307123852823]; Research Grants Council, University Grants Committee [CityU 11101518].