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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 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.

SUBMITTER: Schmidt FL 

PROVIDER: S-EPMC7925540 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement.

Schmidt Frederik L FL   Sürth Valerie V   Berg Tim K TK   Lin Yi-Pin YP   Hovius Joppe W JW   Kraiczy Peter P  

Scientific reports 20210302 1


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. F  ...[more]

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