Structure-Activity Guided Innovation of Antibacterial Strategies
Our research interests are in the relation of protein function to macromolecular structure. We are integrating X-ray crystallography with microbiology and biochemistry to answer questions about toxin-antitoxin systems and other proteins, and their roles in bacteria that cause human disease.
Analysis of Type II Toxin-Antitoxin Systems in Bacteria
This work focuses on understanding the mechanistic details of the RelE/ParE structural family. Our emphasis is on ParE toxin inhibition of DNA gyrase, the impact this has on bacterial cells, and the potential to use this in a novel therapeutic approach. Our work is leading the field in understanding the roles for these TA systems.
We have found that chromosomally-encoded ParE toxins have an attenuated activity, providing a window for bacterial cells to co-opt this into pathways for homeostasis. Current investigations are evaluating a role for this activity in driving mutations during adaptation, a known risk factor in the development of antimicrobial resistance.