Fluorescence Assessment of the AmpR-Signaling Network of Pseudomonas aeruginosa to Exposure to β-Lactam Antibiotics

ACS Chem Biol. 2020 May 15;15(5):1184-1194. doi: 10.1021/acschembio.9b00875. Epub 2020 Feb 10.

Abstract

Gram-negative bacteria have evolved an elaborate pathway to sense and respond to exposure to β-lactam antibiotics. The β-lactam antibiotics inhibit penicillin-binding proteins, whereby the loss of their activities alters/damages the cell-wall peptidoglycan. Bacteria sense this damage and remove the affected peptidoglycan into complex recycling pathways. As an offshoot of these pathways, muropeptide chemical signals generated from the cell-wall recycling manifest the production of a class C β-lactamase, which hydrolytically degrades the β-lactam antibiotic as a resistance mechanism. We disclose the use of a fluorescence probe that detects the activation of the recycling system by the formation of the key muropeptides involved in signaling. This same probe additionally detects natural-product cell-wall-active antibiotics that are produced in situ by cohabitating bacteria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Bacterial Proteins / metabolism*
  • Biological Products / metabolism
  • Cell Wall / metabolism
  • Fluorescent Dyes / chemistry*
  • Metabolome / drug effects
  • Optical Imaging / methods*
  • Penicillin-Binding Proteins / metabolism
  • Pseudomonas aeruginosa / drug effects*
  • Signal Transduction
  • beta-Lactam Resistance / drug effects
  • beta-Lactams / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Biological Products
  • Fluorescent Dyes
  • Penicillin-Binding Proteins
  • beta-Lactams
  • AmpR protein, Bacteria