Fluorescence Assessment of the AmpR-Signaling Network of to Exposure to β-Lactam Antibiotics.
David A Dik, Choon Kim, Chinedu S Madukoma, Jed F Fisher, Joshua D Shrout, Shahriar Mobashery
Author Information
David A Dik: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
Choon Kim: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
Chinedu S Madukoma: Department of Civil & Environmental Engineering & Earth Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
Jed F Fisher: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
Joshua D Shrout: Department of Civil & Environmental Engineering & Earth Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
Shahriar Mobashery: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States. ORCID
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 by cohabitating bacteria.
References
J Am Chem Soc. 2015 Jan 14;137(1):190-200
[PMID: 25495032]
