Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement
Abstract Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and V...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84533-x |
| _version_ | 1818998165304508416 |
|---|---|
| author | Frederik L. Schmidt Valerie Sürth Tim K. Berg Yi-Pin Lin Joppe W. Hovius Peter Kraiczy |
| author_facet | Frederik L. Schmidt Valerie Sürth Tim K. Berg Yi-Pin Lin Joppe W. Hovius Peter Kraiczy |
| author_sort | Frederik L. Schmidt |
| collection | DOAJ |
| description | Abstract Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi. |
| first_indexed | 2024-12-20T21:57:11Z |
| format | Article |
| id | doaj.art-59628b0231514b988122a365c9762cee |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:57:11Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-59628b0231514b988122a365c9762cee2022-12-21T19:25:25ZengNature PortfolioScientific Reports2045-23222021-03-0111111310.1038/s41598-021-84533-xInteraction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complementFrederik L. Schmidt0Valerie Sürth1Tim K. Berg2Yi-Pin Lin3Joppe W. Hovius4Peter Kraiczy5Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe UniversityInstitute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe UniversityInstitute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe UniversityDivision of Infectious Diseases, Wadsworth Center, New York State Department of HealthCenter for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam Infection and Immunity InstituteInstitute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe UniversityAbstract Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.https://doi.org/10.1038/s41598-021-84533-x |
| spellingShingle | Frederik L. Schmidt Valerie Sürth Tim K. Berg Yi-Pin Lin Joppe W. Hovius Peter Kraiczy Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement Scientific Reports |
| title | Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement |
| title_full | Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement |
| title_fullStr | Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement |
| title_full_unstemmed | Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement |
| title_short | Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement |
| title_sort | interaction between borrelia miyamotoi variable major proteins vlp15 16 and vlp18 with plasminogen and complement |
| url | https://doi.org/10.1038/s41598-021-84533-x |
| work_keys_str_mv | AT frederiklschmidt interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement AT valeriesurth interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement AT timkberg interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement AT yipinlin interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement AT joppewhovius interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement AT peterkraiczy interactionbetweenborreliamiyamotoivariablemajorproteinsvlp1516andvlp18withplasminogenandcomplement |