Pentamidine sensitizes FDA-approved non-antibiotics for the inhibition of multidrug-resistant Gram-negative pathogens

Pentamidine sensitizes FDA-approved antibiotics to combat Gram-negative pathogens. We screened 1374 FDA-approved non-antibiotics for their ability to be sensitized by pentamidine against Escherichia coli . We identified mitomycin C and mefloquine as potent hits effective against multiple drug-resistant, Gram-negative bacteria. Killing kinetics and an in vivo model with Caenorhabditis elegans ( C. elegans ) revealed that such combinations produced synergy against colistin-resistant Enterobacter cloacae ( E. cloacae ). These findings suggest combinations of FDA-approved non-antibiotics, and pentamidine can be repurposed into new antimicrobial agents.