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）是人类鼻咽部的正常定植菌，可引发严重的侵袭性疾病。由于鼻咽部定植是进展为侵袭性疾病的先决条件，未来研发蛋白类疫苗需阐明细菌黏附素与宿主受体的紧密互作机制。本研究中，我们鉴定发现：肺炎链球菌表面黏附素A（PsaA）——一种已知在肺炎链球菌定植过程中发挥关键作用的高度保守蛋白——可与Detroit 562鼻咽上皮细胞表面的膜联蛋白A2（ANXA2）发生特异性互作。在本底ANXA2表达量极低的HEK 293 T/17细胞中通过慢病毒介导过表达ANXA2，可显著增强肺炎链球菌的黏附能力；而利用重组PsaA阻断ANXA2，则会显著削弱肺炎链球菌对经ANXA2慢病毒转导的HEK细胞的黏附能力。上述结果表明，ANXA2是介导肺炎链球菌定植的重要宿主细胞受体。