Tsang J C, Weber D A, Brown D A
J Antibiot (Tokyo). 1976 Jul;29(7):735-42. doi: 10.7164/antibiotics.29.735.
In vitro and in vivo complex formations of polymyxin B and lipopolysaccharides (LPS) from resistant and sensitive cells of Serratia marcescens were studied by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and electron microscopy. In vitro treatment of LPS from resistant cells with polymyxin B gave two populations of spherical complexes of differnt molecular weights as determined electrophoretically. Similar treatment of LPS from sensitive cells resulted in dissociation of the LPS-protein and subsequent complexing with the LPS moiety into stable spheres. In vivo treatment of resistant cells with polymyxin B resulted in LPS-polymyxin B complexes which were comparatively smaller and existed in two morphological forms; spheres and linear ribbons. LPS from the sensitive cells were degraded extensively into small rods and an amorphous mass by the in vivo polymyxin B treatment. In both systems, the electrophoretic results consistently matched the electron microscopic evidences for complex formation of LPS with polymyxin B. It is suggested that the disruptive effects of polymyxin B on LPS in the outer membrane of S. marcescens may be the explanation for the change in permeability barrier in the resistant cells and disorganization of the outer membrane and subsequent death in the sensitive cells. Furthermore, the ability of the LPS to complex with the polymyxin B molecules in resistant cells may be the basis of their resistance to the antibiotic.
通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳和电子显微镜,研究了多粘菌素B与粘质沙雷氏菌耐药细胞和敏感细胞的脂多糖(LPS)在体外和体内形成的复合物。用多粘菌素B对耐药细胞的LPS进行体外处理,电泳测定得到了两种分子量不同的球形复合物群体。对敏感细胞的LPS进行类似处理,导致LPS-蛋白质解离,随后LPS部分形成稳定的球体。用多粘菌素B对耐药细胞进行体内处理,产生了LPS-多粘菌素B复合物,其相对较小,存在两种形态;球体和线性条带。用多粘菌素B对敏感细胞进行体内处理,其LPS被广泛降解为小棒状物和无定形物质。在这两个系统中,电泳结果与LPS与多粘菌素B形成复合物的电子显微镜证据一致。有人提出,多粘菌素B对粘质沙雷氏菌外膜中LPS的破坏作用,可能是耐药细胞通透性屏障改变以及敏感细胞外膜解体和随后死亡的原因。此外,耐药细胞中LPS与多粘菌素B分子形成复合物的能力,可能是它们对抗生素耐药的基础。