Fluorescent Triazole Urea Activity‐Based Probes for the Single‐Cell Phenotypic Characterization of Staphylococcus aureus. (22nd March 2019)

• Record Type: Journal Article
• Authors: Chen, Linhai; Keller, Laura J.; Cordasco, Edward; Bogyo, Matthew; Lentz, Christian S.
• Is Part Of: Angewandte Chemie. Volume 131:Number 17(2019)
• Page Start: 5699
• Page End: 5703
• Publication Date: 2019-03-22
• Subjects: Aktivitätsbasierte Sonden -- Einzelzellanalyse -- Enzyme -- Molekulare Bildgebung -- Protein-Profiling; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201900511
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Phenotypically distinct cellular (sub)populations are clinically relevant for the virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells are usually indistinguishable from each other. Herein, we introduce fluorescent activity‐based probes as chemical tools for the single‐cell phenotypic characterization of enzyme activity levels in Staphylococcus aureus . We screened a 1, 2, 3‐triazole urea library to identify selective inhibitors of fluorophosphonate‐binding serine hydrolases and lipases in S. aureus and synthesized target‐selective activity‐based probes. Molecular imaging and activity‐based protein profiling studies with these probes revealed a dynamic network within this enzyme family involving compensatory regulation of specific family members and exposed single‐cell phenotypic heterogeneity. We propose the labeling of enzymatic activities by chemical probes as a generalizable method for the phenotyping of bacterial cells at the population and single‐cell level.