Our team uses protein engineering and chemical synthesis to improve proteins to combat multidrug-resistant bacteria. We study muralytic proteins, as they have been shown to kill bacteria without triggering resistance pathways. Skills that students gain from the Williams lab include molecular cloning, organic synthesis, and imaging. For an overview of our research interests, please see view the video!

Multidrug-resistant bacteria are one of the leading causes of illness and death in the United States. Despite the development of small molecule drugs to combat these harmful bugs, bacteria have evolved to escape death. A promising alternative to synthetic drugs is CHAPK. CHAPK is an enzyme that kills bacteria by breaking down their cell walls. However before being used by the general public, improvements to their activity are necessary. To this end, protein engineering will be used to increase CHAPK activity. A fluorogenic assay with synthetic peptides will be developed to assess activity in a high-throughput manner. Work in this area will advance the development of antibiotics against drug-resistant pathogens, and further studies will focus on optimizing activity.

Endolysins, or hydrolytic enzymes, have been of recent interest for treating drug-resistant bacterial infections. Treatment occurs through degradation of the peptidoglycan layer of the cell, followed by cell lysis. While it is well-known where these endolysins cut, it is unclear why it cleaves at those specific sites. In this work, we're using CHAPK to explore the mechanism of cleavage. Using fluorogenic peptides, we can preform a biochemical analysis of CHAPK with different cleavage sites. Work in this area will provide more insight to how to rationally improve activity of endolysins and new avenues for controlling bacterial targets.