Single-cell phenotypic characterization of Staphylococcus aureus with fluorescent triazole urea activity-based probes.
dc.contributor.author | Chen, Linhai | |
dc.contributor.author | Keller, Laura J | |
dc.contributor.author | Cordasco, Edward A | |
dc.contributor.author | Bogyo, Matthew | |
dc.contributor.author | Lentz, Christian S | |
dc.date.accessioned | 2019-03-14T08:51:02Z | |
dc.date.available | 2019-03-14T08:51:02Z | |
dc.date.issued | 2019-02-15 | |
dc.identifier.citation | Angew Chem Int Ed Engl. 2019 Feb 15. doi: 10.1002/anie.201900511. | en_US |
dc.identifier.issn | 1521-3773 | |
dc.identifier.pmid | 30768830 | |
dc.identifier.doi | 10.1002/anie.201900511 | |
dc.identifier.uri | http://hdl.handle.net/10033/621721 | |
dc.description.abstract | Phenotypically distinct cellular (sub)populations are clinically relevant for virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells are usually indistinguishable from each other. Here, we introduce fluorescent activity-based probes as chemical tools for 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 chemical probe labeling of enzymatic activities as a generalizable method for phenotyping of bacterial cells at the population and single-cell level. | en_US |
dc.publisher | Wiley-Blackwell | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Activity-based protein profiling | en_US |
dc.subject | Molecular Imaging | en_US |
dc.subject | Phenotype | en_US |
dc.subject | enzymes | en_US |
dc.subject | single-cell analysis | en_US |
dc.title | Single-cell phenotypic characterization of Staphylococcus aureus with fluorescent triazole urea activity-based probes. | en_US |
dc.type | Article | en_US |
dc.contributor.department | HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany. | en_US |
dc.identifier.journal | Angewandte Chemie - International Edition | en_US |
dc.identifier.pmcid | PMC6456404 | en |
refterms.dateFOA | 2020-02-15T00:00:00Z | |
dc.source.journaltitle | Angewandte Chemie (International ed. in English) |