Why we care
Highly drug-resistant bacteria are a major threat to global health; these bacteria have outpaced the development of new antimicrobials and in some cases utilize broad resistance mechanisms that are challenging to overcome. A recent economic review estimated that, unless we take corrective action, by 2050 drug-resistant infections will cause more deaths than cancer. We study a key biochemical problem of clinical relevance relating to drug-resistant Enterobacteriaeceae: understanding the changes necessary and sufficient for beta-lactamase enzymes to acquire carbpanemase activity, and more generally to resist new therapeutic compounds targeting this pathway.
What we do
Work in the lab focuses on two areas: better means of detecting drug-resistant infections and way to predict resistance mutations so that we can develop new drugs against them. Using molecular dynamics simulations followed by experimental mutagenesis and enzymology, we have identified a number of allosteric mutations that increase resistance against commonly used antibiotics.