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首页> 外文期刊>EBioMedicine >The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates
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The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates

机译:肺炎球菌α-甘油磷酸磷酸酶通过结合宿主糖缀合物增强鼻咽定植。

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Abstract Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lactoeolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.
机译:摘要肺炎链球菌(肺炎球菌)是一种主要的人类病原体,引起多种疾病,包括中耳炎,肺炎,菌血症和脑膜炎。在这里,我们检查了潜在的肺炎球菌脑膜炎疫苗抗原,α-甘油磷酸氧化酶(SpGlpO)在鼻咽定植中的作用。我们发现SpGlpO缺陷的血清型4和血清型6A菌株在小鼠鼻咽中定植的能力显着降低,并且在体外对人鼻咽癌细胞的粘附性显着缺陷。我们还证明了用重组SpGlpO进行鼻内免疫可显着保护小鼠免受野生型4型血清型和6A型血清型菌株随后的鼻部定植。此外,我们显示,SpGlpO与包含GlcNAcβ1-3Galβ二糖的乳糖/神经氨酸/神经节宿主聚糖结构牢固结合,表明SpGlpO通过结合宿主糖缀合物增强了鼻咽的定植。我们建议SpGlpO是针对肺炎球菌携带的有前途的疫苗候选者,并保证将其包含在多组分蛋白疫苗制剂中,该制剂可针对各种形式的肺炎球菌疾病提供可靠的,不依赖血清型的保护。

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