Lysine Residues in the MK-Rich Region Are Not Required for Binding of the PbsP Protein From Group B Streptococci to Plasminogen

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.

Automated summary

The study identified the importance of Plg's K4 Kringle domain in binding to the bacterial protein PbsP, with lysine binding sites in the Plg molecule playing a key role in the interaction. Interestingly, mutating lysine residues in PbsP did not decrease its ability to bind Plg, indicating a novel bacterial sequence that can interact with lysine binding sites in the Plg molecule.