Drug-resistant bacteria

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.

comparative_deaths_1
Projected increase in deaths from antimicrobial-resistant infections (AMR).  Review on Antimicrobial Resistance, http://amr-review.org

 

 

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.

We have also developed ways to predict how well antibiotic candidates can get into bacteria.  Read our latest manuscript in the publications section!