Department of Sciences, University 'Roma Tre', Rome, Italy.
Department of Sciences, University 'Roma Tre', Rome, Italy; Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Int J Antimicrob Agents. 2019 Apr;53(4):449-455. doi: 10.1016/j.ijantimicag.2018.11.008. Epub 2018 Nov 23.
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.
细菌耐药性的增加危及了目前控制感染的治疗策略，因此需要开发具有新作用机制的新型抗菌药物。本研究报告了 3-溴丙酮酸（3BP）在抗葡萄球菌方面的强大和选择性活性，3BP 是一种处于临床前开发阶段的抗癌药物的代谢物。3BP 对金黄色葡萄球菌具有杀菌活性，其有效浓度与报道的有效抗癌细胞的浓度相当。相比之下，3BP 对其他 ESKAPE 细菌（粪肠球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属）没有相关活性。使用包括多药耐药株在内的人类和兽医菌株的小组证实了 3BP 的抗葡萄球菌活性。3BP 在增加其稳定性的条件下（酸性 pH 值）或促进金黄色葡萄球菌发酵代谢（厌氧条件）下显示出最高的抗菌活性，尽管 3BP 也能够杀死代谢不活跃的细胞。3BP 与庆大霉素表现出协同作用，并且在浓度仅略高于抑制浮游细胞的浓度时，还破坏了已形成的金黄色葡萄球菌生物膜。本研究揭示了抗癌药物 3BP 的新型抗菌和抗生物膜活性，为进一步的临床前研究铺平了道路。
