A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance

Mol Cell Proteomics. 2018 Dec;17(12):2496-2507. doi: 10.1074/mcp.RA118.000880. Epub 2018 Sep 19.

Abstract

The rapid emergence of antimicrobial resistance is a major threat to human health. Antibiotics modulate a wide range of biological processes in bacteria and as such, the study of bacterial cellular signaling could aid the development of urgently needed new antibiotic agents. Due to the advances in bacterial phosphoproteomics, such a systemwide analysis of bacterial signaling in response to antibiotics has recently become feasible. Here we present a dynamic view of differential protein phosphorylation upon antibiotic treatment and antibiotic resistance. Most strikingly, differential phosphorylation was observed on highly conserved residues of resistance regulating transcription factors, implying a previously unanticipated role of phosphorylation mediated regulation. Using the comprehensive phosphoproteomics data presented here as a resource, future research can now focus on deciphering the precise signaling mechanisms contributing to resistance, eventually leading to alternative strategies to combat antimicrobial resistance.

Keywords: Bacteria; Microbiology; Pathogens; Phosphorylation; Quantification; antimicrobial resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Chromatography, Liquid
  • Drug Resistance, Multiple, Bacterial*
  • Escherichia coli / drug effects*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins
  • Humans
  • Phosphorylation
  • Proteomics / methods
  • Signal Transduction / drug effects*
  • Tandem Mass Spectrometry
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Escherichia coli Proteins
  • MCR-1 protein, E coli
  • Transcription Factors