细菌耐药性对公众健康构成严重威胁；预计到 2050 年，多重耐药 (MDR) 细菌感染将增加 14 倍。与抗生素相反，联合疗法是抗病毒和抗癌治疗的标准治疗方法，因为协同药物相互作用可以降低剂量和耐药性发展。在这项研究中，我们在协同研究中研究了一种新型琥珀酸脱氢酶抑制剂（原米沙林）与特定代谢和外排抑制剂以及一组临床批准的抗生素的联合治疗。通过这些研究，我们确定原米沙林在亚抑制浓度下可以与万古霉素协同作用，并与氨基糖苷类和乙醛酸分流途径抑制剂拮抗作用。然而，这些协同效应不会降低最低抑制浓度。这些结果的可变性强调了抗生素开发中联合疗法的靶向代谢的复杂性。

Antibacterial resistance poses a severe threat to public health; an anticipated 14-fold increase in multidrug-resistant (MDR) bacterial infections is expected to occur by 2050. Contrary to antibiotics, combination therapies are the standard of care for antiviral and anticancer treatments, as synergistic drug-drug interactions can decrease dosage and resistance development. In this study, we investigated combination treatments of a novel succinate dehydrogenase inhibitor (promysalin) with specific inhibitors of metabolism and efflux alongside a panel of clinically approved antibiotics in synergy studies. Through these investigations, we determined that promysalin can work synergistically with vancomycin and antagonistically with aminoglycosides and a glyoxylate shunt pathway inhibitor at subinhibitory concentrations; however, these cooperative effects do not reduce minimum inhibitory concentrations. The variability of these results underscores the complexity of targeting metabolism for combination therapies in antibiotic development.