Department of Biomedical, Dental and Imaging Sciences, University of Messina, Messina, Italy.
Department of Human Pathology and Medicine, University of Messina, Messina, Italy.
Front Cell Infect Microbiol. 2021 Sep 8;11:679792. doi: 10.3389/fcimb.2021.679792. eCollection 2021.
Binding to plasminogen (Plg) enables bacteria to associate with and invade host tissues. The cell wall protein PbsP significantly contributes to the ability of group B streptococci, a frequent cause of invasive infection, to bind Plg. Here we sought to identify the molecular regions involved in the interactions between Plg and PbsP. The K4 Kringle domain of the Plg molecule was required for binding of Plg to whole PbsP and to a PbsP fragment encompassing a region rich in methionine and lysine (MK-rich domain). These interactions were inhibited by free L-lysine, indicating the involvement of lysine binding sites in the Plg molecule. However, mutation to alanine of all lysine residues in the MK-rich domain did not decrease its ability to bind Plg. Collectively, our data identify a novel bacterial sequence that can interact with lysine binding sites in the Plg molecule. Notably, such binding did not require the presence of lysine or other positively charged amino acids in the bacterial receptor. These data may be useful for developing alternative therapeutic strategies aimed at blocking interactions between group B streptococci and Plg.
纤溶酶原（Plg）的结合使细菌能够与宿主组织结合并入侵。细胞壁蛋白 PbsP 显著促进 B 群链球菌（一种常见的侵袭性感染原因）结合 Plg 的能力。在这里，我们试图确定 Plg 和 PbsP 之间相互作用涉及的分子区域。Plg 分子的 K4 结构域对于 Plg 与整个 PbsP 和包含富含甲硫氨酸和赖氨酸（MK-丰富结构域）的区域的 PbsP 片段的结合是必需的。这些相互作用被游离 L-赖氨酸抑制，表明 Plg 分子中存在赖氨酸结合位点。然而，将 MK-丰富结构域中所有赖氨酸残基突变为丙氨酸并没有降低其结合 Plg 的能力。总之，我们的数据确定了一种新型细菌序列，它可以与 Plg 分子中的赖氨酸结合位点相互作用。值得注意的是，这种结合不需要细菌受体中存在赖氨酸或其他带正电荷的氨基酸。这些数据可能对开发旨在阻断 B 群链球菌与 Plg 之间相互作用的替代治疗策略有用。
