The antimetabolite 3-bromopyruvate selectively inhibits Staphylococcus aureus
2019
Visca, Paolo | Pisa, Federica | Imperi, Francesco
Increased antibacterial resistance jeopardizes current therapeutic strategies to control infections, soliciting the development of novel antibacterial drugs with new mechanisms of action. This study reports the discovery of potent and selective antistaphylococcal activity of 3-bromopyruvate (3BP), an antimetabolite in preclinical development as an anticancer drug. 3BP showed bactericidal activity against Staphylococcus aureus, with active concentrations comparable with 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 antistaphylococcal activity of 3BP was confirmed using a panel of human and veterinary strains, including multi-drug-resistant isolates. 3BP showed highest antibacterial activity under conditions that increase its 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 antibiofilm activities for the anticancer drug 3BP, paving the way for further preclinical studies.
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