ABSTRACT

Streptococcus pneumoniae (pneumococcus) is a normal colonizer of the human nasopharynx capable of causing serious invasive disease. Since colonization of the nasopharynx is a prerequisite for progression to invasive diseases, the development of future protein-based vaccines requires an understanding of the intimate interaction of bacterial adhesins with host receptors. In this study, we identified that pneumococcal surface adhesin A (PsaA), a highly conserved pneumococcal protein known to play an important role in colonization of pneumococcus, can interact with Annexin A2 (ANXA2) on Detroit 562 nasopharyngeal epithelial cells. Lentiviral expression of ANXA2 in HEK 293 T/17 cells, which normally express minimal ANXA2, significantly increased pneumococcal adhesion. Blocking of ANXA2 with recombinant PsaA negatively impacted pneumococcal adherence to ANXA2-transduced HEK cells. These results suggest that ANXA2 is an important host cellular receptor for pneumococcal colonization.

摘要

肺炎链球菌（肺炎球菌）是人类鼻咽部的正常定植菌，能够引起严重的侵袭性疾病。由于鼻咽部的定植是侵袭性疾病进展的先决条件，因此未来基于蛋白质的疫苗的开发需要了解细菌粘附素与宿主受体的密切相互作用。在这项研究中，我们发现肺炎球菌表面粘附素 A (PsaA) 是一种高度保守的肺炎球菌蛋白，已知在肺炎球菌定植中起重要作用，可与 Detroit 562 鼻咽上皮细胞上的膜联蛋白 A2 (ANXA2) 相互作用。HEK 293 T/17 细胞中 ANXA2 的慢病毒表达显着增加了肺炎球菌粘附，HEK 293 T/17 细胞通常表达最少的 ANXA2。用重组 PsaA 阻断 ANXA2 会对肺炎球菌对 ANXA2 转导的 HEK 细胞的粘附产生负面影响。这些结果表明 ANXA2 是肺炎球菌定植的重要宿主细胞受体。