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Updated: Mar 23, 2026

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
Structure-Resistance Relationships: Interrogating Antiseptic Resistance in Bacteria with Multicationic Quaternary
Megan E Forman1, Madison H Fletcher2, Megan C Jennings2
1Department of Chemistry, Villanova University, 800 East Lancaster Avenue, Villanova, PA, 19085, USA.
Abstract:
Bacterial resistance toward commonly used biocides is a widespread yet underappreciated problem, one which needs not only a deeper understanding of the mechanisms by which resistance proliferates, but also means for mitigation. To advance our understanding of this issue, we recognized a polyaromatic structural core analogous to activators of QacR, a negative transcriptional regulator of the efflux pump QacA, and envisioned a series of quaternary ammonium compounds (QACs) based on this motif. Using commercially available dye scaffolds, we synthesized and evaluated the antimicrobial activity of 52 novel QACs bearing 1-3 quaternary ammonium centers. Striking differences in antimicrobial activity against bacteria bearing QAC resistance genes have been observed, with up to a 125-fold increase in minimum inhibitory concentration (MIC) for select structures against bacteria known to bear efflux pumps. Based on these findings, general trends in structure-resistance relationships have been identified, laying the groundwork for future mechanistic studies.
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