Centre for New Antibacterial Strategies (CANS) seminar

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. In this talk Lentz will report on his recent efforts to overcome this limitation by developing fluorescent activity-based probes (i.e. functionalized enzyme inhibitors) as chemical tools for single-cell phenotypic characterization of enzyme activity levels in Staphylococcus aureus. His group screened various chemical libraries to identify selective inhibitors of serine hydrolases in S. aureus and converted hit inhibitors into target-selective activity-based probes. Molecular imaging and chemical proteomics studies with these probes identified a new virulence factor involved in tissue-specific infection in a systemic mouse model of S. aureus infection, revealed a dynamic enzymatic network involving compensatory regulation of specific family members, and exposed single-cell phenotypic heterogeneity. Current activities focus on the establishment of chemical probe labeling of enzymatic activities as a generalizable method for phenotyping of bacterial cells at the population and single-cell level.