Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide
that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing
is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting
further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in
the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug
Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens.
The in vitro screening identified 49 non-antimicrobial drugs that were active against at least one species of
ESKAPE pathogen. Although some of these drugs were known to have antibacterial activity, many have never
been reported before. In particular, sulfonamide-containing structures represent a novel drug scaffold that should
be investigated further. The characteristics of these drugs as antimicrobial agents may offer a safe, effective, and
quick supplement to current approaches to treating bacterial infections.