Fighting Superbugs: New Ways to Disrupt Drug Resistance

A world where antibiotics can't keep up with the bugs they're designed to fight. That's the challenge posed by carbapenemase-producing Enterobacterales (CPEs), a group of multidrug-resistant pathogens that are becoming increasingly hard to treat. These bacteria have plasmids, which are like tiny, portable DNA libraries that make them resistant to even our strongest antibiotics, including carbapenems. Scientists have been on the hunt for compounds that can disrupt these resistance-conferring plasmids. One promising candidate, CGS-15943, was identified through a high-throughput screening process using a synthetic plasmid introduced into Escherichia coli K-12 tolC cells. However, CGS-15943 didn't work in regular E. coli, suggesting that it was being kicked out by the bacteria's efflux pumps.To tackle this problem, researchers created analogues of CGS-15943. These new compounds were designed to be more effective and to overcome the efflux issue seen in regular E. coli. Two of these analogues showed much better activity against the plasmids in E. coli tolC mutants, while one compound even worked moderately well in regular E. coli at low concentrations. This is a big deal because it suggests that we might be able to find ways to make our antibiotics more effective again. It's like outsmarting the bacteria by targeting their resistance tools directly.