Open AccessFluorescence Assessment of the AmpR-Signaling Network of Pseudomonas aeruginosa to Exposure to β-Lactam Antibiotics
Author(s) -
David A. Dik,
Choon Kim,
Chinedu S. Madukoma,
Jed F. Fisher,
Joshua D. Shrout,
Shahriar Mobashery
Publication year - 2020
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.9b00875
Subject(s) - peptidoglycan , antibiotics , pseudomonas aeruginosa , bacteria , cell wall , microbiology and biotechnology , penicillin binding proteins , penicillin , lactam , bacterial cell structure , chemistry , biochemistry , gram negative bacteria , biology , gene , escherichia coli , stereochemistry , genetics
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.