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Surface Antigen Exposure by Bismuth Dimercaprol Suppression of Klebsiella pneumoniae Capsular Polysaccharide

机译:铋二巯基吡咯抑制肺炎克雷伯菌荚膜多糖的表面抗原暴露。

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The bacterial capsule is an important virulence determinant in animal and plant disease. Bacterial capsule and slime can be inhibited by bismuth compounds, especially when complexed with lipophilic thiol chelators. Bismuth dimercaprol (BisBAL) at 1 ppm of Bi3+repressed Klebsiella pneumoniae capsule expression in defined medium by nearly 90%, which exposed subsurface structures. The phagocytic index for BisBAL-treated bacteria increased from <10 to 360 bacteria per 100 neutrophils in the presence of complement and anticapsular or anti-O antigen antiserum. BisBAL treatment also enhanced the reactivity of monoclonal antibodies (MAbs) specific for the O1-antigen lipopolysaccharide (LPS) or the LPS core in a dose-dependent manner as indicated by the results of enzyme-linked immunosorbent assays. When anti-O1 MAb was used, the reactivity increased significantly for fully encapsulated O1:K1 or O1:K2 cells but not for O1:K? cells. Deposition of C3b also increased significantly for BisBAL-treated O1:K1 or O1:K2 cells but not for O1:K? cells. Survival of a serum-sensitive strain was <0.1% when nonimmune human serum absorbed with O1:K1 cells was used and 107% when BisBAL-treated cells were used for absorption. Outer membrane proteins were also more accessible on the surface of K. pneumoniae after BisBAL treatment. Thus, at subinhibitory levels, BisBAL inhibited capsule expression, which promoted phagocytosis, enhanced the reactivity of specific antibodies for LPS O antigen, LPS core epitopes, or outer-membrane proteins, and enhanced complement interaction with encapsulated K. pneumoniae. By unmasking bacterial surface structures and enhancing the immune system reactivity to bacteria, bismuth thiols may prove useful as adjuncts for vaccination.
机译:细菌荚膜是动植物疾病中重要的毒力决定因素。铋化合物可抑制细菌的囊和粘液,特别是与亲脂性硫醇螯合剂复合时。 Bi 3 + 在1 ppm处的二巯基铋(BisBAL)在确定的培养基中抑制肺炎克雷伯菌的胶囊表达近90%,从而暴露了地下结构。在存在补体和抗荚膜或抗O抗原抗血清的情况下,BisBAL处理的细菌的吞噬指数从每10个中性粒细胞<10个细菌增加到360个细菌。如酶联免疫吸附测定的结果所示,BisBAL处理还以剂量依赖的方式增强了对O1抗原脂多糖(LPS)或LPS核心特异的单克隆抗体(MAb)的反应性。当使用抗O1 MAb时,完全包封的O1:K1或O1:K2细胞的反应性显着增加,而O1:K ?细胞则没有。 BisBAL处理的O1:K1或O1:K2细胞的C3b沉积也显着增加,而O1:K ?细胞则没有。当使用被O1:K1细胞吸收的非免疫人血清时,血清敏感性菌株的存活率<0.1%,而当使用BisBAL处理的细胞进行吸收时,其存活率<107%。在 K的表面上,外膜蛋白也更容易接近。 BisBAL治疗后出现肺炎。因此,在亚抑制水平,BisBAL抑制胶囊表达,从而促进吞噬作用,增强了针对LPS O抗原,LPS核心表位或外膜蛋白的特异性抗体的反应性,并增强了与封装的 K的补体相互作用。肺炎。通过揭露细菌表面结构并增强免疫系统对细菌的反应性,铋硫醇可被证明是疫苗接种的辅助剂。

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