Pneumococcal surface adhesion A protein (PsaA) interacts with human Annexin A2 on airway epithelial cells

<i>Streptococcus pneumoniae</i> (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.

肺炎链球菌（Streptococcus pneumoniae，又称肺炎球菌）是人类鼻咽部的正常定植菌，可引发严重侵袭性疾病。由于鼻咽部定植是进展为侵袭性疾病的先决条件，未来开发蛋白疫苗需阐明细菌黏附素与宿主受体的紧密互作机制。本研究发现，已知在肺炎球菌定植中发挥关键作用的高度保守肺炎球菌蛋白——肺炎球菌表面黏附素A（PsaA），可与Detroit 562鼻咽上皮细胞表面的膜联蛋白A2（ANXA2）产生互作。在本底表达量极低的HEK 293 T/17细胞中通过慢病毒介导过表达ANXA2，可显著增强肺炎球菌的黏附能力；而使用重组PsaA阻断ANXA2，则会抑制肺炎球菌对ANXA2转导的HEK细胞的黏附。上述结果表明，ANXA2是参与肺炎球菌定植的重要宿主细胞受体。