Leptospiral endostatin-like protein A is a bacterial cell surface receptor for human plasminogen.
The spirochete Leptospira interrogans is a highly invasive pathogen of worldwide public health importance. Studies from our laboratories and another have demonstrated that L. interrogans can acquire host plasminogen on its surface. Exogenous plasminogen activators can then convert bound plasminogen into the functionally active protease plasmin. In this study, we extend upon those observations and report that leptospiral endostatin-like protein A (LenA) binds human plasminogen in a dose-dependent manner. LenA-plasminogen interactions were significantly inhibited by the lysine analog xi-aminocaproic acid, suggesting that the lysine-binding sites on the amino-terminal kringle portion of the plasminogen molecule play a role in the binding. Previous studies have shown that LenA also binds complement regulator factor H and the extracellular matrix component laminin. Plasminogen competed with both factor H and laminin for binding to LenA, which suggests overlapping ligand-binding sites on the bacterial receptor. Finally, LenA-bound plasminogen could be converted to plasmin, which in turn degraded fibrinogen, suggesting that acquisition of host-derived plasmin by LenA may aid bacterial dissemination throughout host tissues.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, MN 469 Chandler Medical Center, Lexington, KY 40536-0298, USA. ashutosh.verma@uky.edu
Ashutosh
A
Verma
Catherine A
CA
Brissette
Amy A
AA
Bowman
Samir T
ST
Shah
Peter F
PF
Zipfel
Brian
B
Stevenson
D000614:Aminocaproates / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000378:metabolism; D007921:Leptospira interrogans / Q000472:pathogenicity*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping
D000614:Aminocaproates; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007797:Laminin; D017242:Complement Factor H; D010958:Plasminogen