GSK Vaccines, Siena.
Institute for Immunology, University of California-Irvine School of Medicine.
J Infect Dis. 2016 Feb 15;213(4):516-22. doi: 10.1093/infdis/jiv461. Epub 2015 Sep 23.
The adhesion of Streptococcus pneumoniae is a key step during colonization of human respiratory tract mucosae. Here we demonstrate that pneumococcal type I pilus significantly increases the adhesiveness of poorly adhering highly capsulated strains in vitro. Interestingly, preincubation of bacteria with antibodies against the major pilus backbone subunit (RrgB) or the adhesin component (RrgA) impaired pneumococcal association to human epithelial cells. Screening for anti-RrgA monoclonal antibodies specifically affecting the adhesive capacity of S. pneumoniae led to the identification of the monoclonal 11B9/61 antibody, which greatly reduced pilus-dependent cell contact. Proteomic-based epitope mapping of 11B9/61 monoclonal antibody revealed a well-exposed epitope on the D2 domain of RrgA as the target of this functional antibody. The data presented here confirm the importance of pilus I for S. pneumoniae pathogenesis and the potential use of antipilus antibodies to prevent bacterial colonization.
肺炎链球菌的黏附是其定植于人呼吸道黏膜的关键步骤。在此我们证明，肺炎球菌 I 型菌毛显著增加了体外黏附性差的高荚膜菌株的黏附性。有趣的是，用针对主要菌毛骨干亚基（RrgB）或黏附素成分（RrgA）的抗体预先孵育细菌，会损害肺炎球菌与人上皮细胞的关联。筛选特异性影响肺炎链球菌黏附能力的抗 RrgA 单克隆抗体，导致了单克隆 11B9/61 抗体的鉴定，该抗体大大降低了依赖菌毛的细胞接触。基于蛋白质组学的 11B9/61 单克隆抗体表位作图显示，RrgA 的 D2 结构域上存在一个暴露良好的表位，是该功能抗体的靶标。本文提供的数据证实了菌毛 I 对于肺炎链球菌发病机制的重要性，以及使用抗菌毛抗体预防细菌定植的潜力。
