TY  - JOUR
A1  - Schmidt, Frederik Lennart
A1  - Sürth, Valerie
A1  - Berg, Tim K.
A1  - Lin, Yi-Pin
A1  - Hovius, Joppe W.
A1  - Kraiczy, Peter
T1  - Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement
T2  - Scientific reports
N2  - 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.
KW  - Diseases
KW  - Immunology
KW  - Microbiology
KW  - Pathogenesis
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63754
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-637547
SN  - 2045-2322
N1  - This work was supported by the LOEWE Center DRUID (Novel Drug Targets against Poverty-Related and Neglected Tropical Infectious Diseases), project C3 and NIH-R01AI121401) to PK, NSF-IOS1755286 and NIH-R21AI144891 (YPL). JWH was supported by a grant from ZonMw (project number 522003007, Ticking on Pandora’s box) and a grant from the EU Interreg North Sea Region program, as part of the NorthTick project. None of the funding agencies had participation in the decision of the study, data collection and analysis, or submission of this work for publications
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 11
IS  - art. 4964
SP  - 1
EP  - 13
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -