Pairing Drugs Kills Pathogens

The antidiarrheal drug Imodium (loperamide hydrochloride) and the alcoholism-aversion drug Antabuse (disulfiram) can both soup up a weak antibiotic called minocycline so that it kills pathogens such as methicillin-resistant Staphylococcus aureus and multi-drug resistant Pseudomonas aeruginosa (Nat. Chem. Biol., DOI: 10.1038/nchembio.559). Motivated by the alarming rise of antibiotic-resistant pathogens and the pharmaceutical industry’s retreat from antibiotic drug discovery, researchers led by Eric D. Brown and Gerard D. Wright at McMaster University, in Hamilton, Ontario, decided to see if some off-patent, nonantibiotic drugs might help minocycline—which several human pathogens are already resistant to—strike out harmful bacteria. Of the 1,057 drug pairs they tested, three of the nonantibiotics worked with minocycline against S. aureus, six such combinations killed P. aeruginosa, and five combinations eradicated Escherichia coli. In the case of the Imodium-minocycline pair, the team found that Imodium didn’t actually kill the harmful bacteria, but it did improve the pathogen’s uptake of minocycline, thereby improving the antibiotic’s potency. These unusual drug duets “show the potential for increasing antibiotic chemical space,” the researchers suggest.