The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.
The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.
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DOI：
10.1016/j.ebiom.2017.03.002
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发表时间：
2017-04
期刊：
影响因子：
11.1
通讯作者：
Ogunniyi AD
中科院分区：
文献类型：
--
作者：
Mahdi LK;Higgins MA;Day CJ;Tiralongo J;Hartley-Tassell LE;Jennings MP;Gordon DL;Paton AW;Paton JC;Ogunniyi AD
肺炎链球菌（肺炎球菌）是一种主要的人类病原体，可引起多种疾病，包括中耳炎、肺炎、菌血症和脑膜炎。在这里，我们研究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。我们发现缺乏SpGlpO的血清型4和血清型6A菌株在小鼠鼻咽部定植的能力显着降低，并且在体外对人鼻咽癌细胞的粘附显着缺陷。我们还证明，用重组 SpGlpO 进行鼻内免疫可显着保护小鼠免受野生型血清型 4 和血清型 6A 菌株随后的鼻定植。此外，我们发现 SpGlpO 与含有 GlcNAcβ1-3Galβ 二糖的乳糖/新乳糖/神经节宿主聚糖结构强烈结合，表明 SpGlpO 通过与宿主糖缀合物的结合增强鼻咽的定植。我们认为 SpGlpO 是一种很有前途的针对肺炎球菌携带疫苗的候选疫苗，并值得纳入多组分蛋白质疫苗配方中，该配方可以为所有形式的肺炎球菌疾病提供强大的、独立于血清型的保护。肺炎链球菌 GlpO (SpGlpO) 通过与特定宿主糖缀合物结合增强小鼠鼻腔定植。 SpGlpO 缺陷的突变体在小鼠鼻咽部的定殖能力较差。 SpGlpO 鼻腔免疫可保护小鼠免受肺炎链球菌定植。迫切需要能够预防鼻腔定植和肺炎链球菌（肺炎球菌）引起的所有形式疾病的新疫苗。在这份手稿中，马赫迪等人。研究表明，α-甘油磷酸氧化酶（SpGlpO）是一种存在于所有肺炎球菌中的蛋白质，通过与特定宿主糖缀合物结合来增强小鼠鼻腔定植，而缺乏 SpGlpO 的菌株在小鼠鼻咽部定植效果较差。 SpGlpO 鼻内免疫可显着保护小鼠免受随后的肺炎链球菌定植，表明 SpGlpO 是一种有前途的针对肺炎球菌携带的蛋白质疫苗候选者。
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 lacto/neolacto/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. Streptococcus pneumoniae GlpO (SpGlpO) enhances nasal colonization of mice through binding to specific host glycoconjugates. Mutants deficient in SpGlpO colonize the mouse nasopharynx poorly. Nasal immunization with SpGlpO protects mice against S. pneumoniae colonization. New vaccines that protect against nasal colonization and all forms of diseases caused by Streptococcus pneumoniae (the pneumococcus) are urgently needed. In this manuscript, Mahdi et al. show that alpha-glycerophosphate oxidase (SpGlpO), a protein present in all pneumococci, enhances nasal colonization of mice through binding to specific host glycoconjugates, and strains lacking SpGlpO colonize the mouse nasopharynx poorly. Intranasal immunization with SpGlpO significantly protects mice against subsequent S. pneumoniae colonization, indicating SpGlpO is a promising protein vaccine candidate against pneumococcal carriage.