The antimetabolite 3-bromopyruvate selectively inhibits Staphylococcus aureus

The rise in antibacterial resistance jeopardizes current therapeutic strategies to control infections, soliciting the development of novel antibacterial drugs with new mechanisms of action. In this work we report the discovery of a potent and selective anti-staphylococcal activity of 3-bromopyruvate (3BP), an antimetabolite in preclinical development phase as an anticancer drug. 3BP showed bactericidal activity against Staphylococcus aureus, with active concentrations comparable to those reported to be effective against cancer cells. In contrast, no relevant activity was observed against other ESKAPE bacteria (Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). The anti-staphylococcal activity of 3BP was confirmed using a panel of human and veterinary strains, including multidrug-resistant isolates. 3BP showed highest antibacterial activity under conditions which increase 3BP stability (acidic pH) or promote S. aureus fermentative metabolism (anaerobiosis), although 3BP was also able to kill metabolically-inactive cells. 3BP showed synergism with gentamicin, and also disrupted preformed S. aureus biofilms, at concentrations only slightly higher than those inhibiting planktonic cells. This study unravels novel antibacterial and anti-biofilm activities for the anticancer drug 3BP, thus paving the way for further pre-clinical studies.