Institute of Anatomy, Faculty of Medicine, University of Bern, 3012 Bern, Switzerland.
Cells. 2022 Jan 5;11(1):166. doi: 10.3390/cells11010166.
The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by and subsp. -important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens.
细菌病原体对抗生素的耐药性不断增加，促使人们开发替代的非抗生素治疗方法。抗病毒疗法既不是抑菌的也不是杀菌的，它通过剥夺细菌病原体的毒力因子来发挥作用。为了建立成功的感染，许多细菌病原体分泌外毒素/细胞溶解素，刺穿宿主细胞膜质。最近开发的脂质体纳米陷阱，模拟靶向细胞膜的外层，作为外毒素的诱饵，从而使它们不再攻击宿主细胞。在这项研究中，我们开发了一种脂质体纳米陷阱配方，能够保护永生化免疫细胞免受 和 亚种分泌的所有细胞溶解素的侵害，这些细胞溶解素是重要的人类病原体，可以导致危及生命的菌血症。我们表明，含有胆固醇的脂质体与仅由磷脂组成的脂质体的混合物可以防止所有链球菌外毒素的联合作用。我们的研究结果为进一步开发脂质体抗病毒疗法铺平了道路，以便为包括由抗生素耐药病原体引起的细菌感染提供更有效的治疗方法。
