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

Gram-negative bacteria have evolved an elaborate pathway to sense and respond to exposure to beta-lactam antibiotics. The beta-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 beta-lactamase, which hydrolytically degrades the beta-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.