Modulation of the Surface-Layer Protein of Clostridium difficile through Cwp84 Inhibition

Cysteine protease Cwp84 is responsible for surface-layer processing in Clostridium difficile and was also shown to cleave several human extracellular matrix components in vitro. To enable the facile identification and characterization of Cwp84 inhibitors, we developed a fluorogenic 10-mer peptide based on the enzyme's natural substrate SlpA that is amenable for use in FRET-based high-throughput screening. The design of substrate-mimetic...