RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model.
CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.
结果:一种高活性鲍曼不动杆菌噬菌体溶素,LysP53与鲍曼不动杆菌相互作用后可以刺激OMV的产生,大肠杆菌,还有沙门氏菌.由鲍曼不动杆菌的溶素(LOMV)制备的OMV显示出更好的均一性,更高的蛋白质产量,较低的内毒素含量,和与天然产生的OMV(nOMV)相比更低的细胞毒性。与nOMV相比,LOMV含有显著较高数量的细胞质和细胞质膜蛋白,但含有较少数量的周质和细胞外蛋白。在肺炎和菌血症小鼠模型中,用LOMVs或nOMVs进行三次肌内免疫可提供针对鲍曼不动杆菌感染的强大保护。鼻内免疫在肺炎模型中提供了良好的保护,但在菌血症模型中提供了较弱的保护(20-40%)。然而,一次免疫接种,在肺炎小鼠模型中,LOMV表现出比nOMV更好的保护作用。
结论:与目前的OMV生产方法相比,新型溶素方法提供了更好的选择,特别是疫苗开发。