Waging War Against Antibiotic Resistance

With antibiotic resistance on the rise, it is increasingly challenging to combat bacterial infections.

With support from a $302,000 National Institutes of Health grant, Chemistry and Biochemistry professors Nina Goodey and David Konas are studying whether a bacterial enzyme might be a viable target for future antibiotics.

The bacterial enzyme IGPS is a catalyst in the synthesis of the essential amino acid tryptophan. “Tryptophan synthesis in bacteria resembles an assembly line,” explains Goodey. “IGPS is the second-to-last worker in this assembly chain. While we know the structures of the starting material and product of the IGPS reaction, we don’t know exactly how IGPS operates.”

Since people — who get their tryptophan from dietary proteins — do not have an IGPS enzyme, Goodey and Konas hypothesize that IGPS could be an effective new target for antibiotics. “We’re excited about the possibility of discovering a compound that will inhibit IGPS with high affinity and allow for studies of IGPS as an antibacterial drug target,” Konas says.

“When we discover a new target, drug resistance will likely eventually emerge, but importantly, the new target buys time to find other new targets and strategies,” says Goodey. “The situation is like an arms race — and we hope scientists, not bacteria, stay on the winning side.”

Many steps will be involved to determine IGPS’s value as an antibacterial target. Konas and his lab will make new compounds that will help the team learn more about IGPS, while Goodey’s lab will produce IGPS enzymes, test the effects of small changes to different parts of the enzymes, and test new compounds with the enzymes.