Franz Lab Takes Aim at Drug Resistance with Metal Binding Agents

New antibacterial strategies are needed to overcome drug resistance in pathogenic bacteria that produce resistance enzymes called metallo-β-lactamases. The Franz lab and graduate student Abbey Jackson recently discovered that their antibacterial prodrug PcephPT is able to inhibit these enzymes. PcephPT, an antibacterial prochelator that releases the metal-binding agent pyrithione (PT) upon cleavage by β-lactamases, inhibits the clinically important metallo-β-lactamase NDM-1 by interacting with the zinc-containing active site. PcephPT restores the activity of a carbapenem antibiotic against NDM-1-expressing E. coli and presents a promising strategy for development of targeted metallo-β-lactamase inhibitors. Read more about this research in ACS Infectious Diseases.