Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens

The study reveals that bacteria expressing metallo-β-lactamases (VIM-2), which are the last-resort antibiotics, have impaired growth in zinc-deprived environments. The researchers identified molecular pathways critical for VIM-2 expression under zinc limitation, revealing that disruption of envelope stress response pathways reduced VIM-2-expressing bacteria’s growth. They also found that VIM-2 expression makes bacteria more susceptible to azithromycin, demonstrating its therapeutic potential against VIM-2-expressing pathogens. This could potentially accelerate the discovery of additional treatments for multidrug-resistant bacteria infections.