A quantitative proteomics approach to monitor targeted protein degradation in M. smegmatis

Targeted protein degradation via the ubiquitin proteasome has been established in eukaryotes, however no application has been shown in bacteria so far. In the present work, selective protein degradation is shown using hetero bifunctional drugs, bringing substrates in close proximity to the bacterial ClpC1P1P2 protein degradation complex. We performed a TMT based quantitative proteomics analysis to monitor degradation of human BRDT in Mycobacterium smegmatis. Our data shows selective degradation of BRDT when using bacterial PROTACS, indicating the first successful application of targeted protein degradation in bacteria.