Interaction of Leptospira membrane proteins with human complement regulators Factor H and C4BP.

Author(s)

Mónica Marcela Castiblanco Valencia

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-09-12

Examining board members

Lourdes Isaac; Enéas de Carvalho; Luis Carlos de Souza Ferreira; Roxane Maria Fontes Piazza; Antonio Carlos Seguro

• Advisor: Lourdes Isaac; Ângela Silva Barbosa

Abstract

Different mechanisms have been shown to be involved in evasion of complement-mediated killing. In this study, we demonstrate that acquisition of FH on the Leptospira surface is crucial for bacterial survival in the serum and that these spirochetes interact with FH, FHL-1, FHR-1 and C4BP. We also demonstrate that binding to these regulators is mediated by leptospiral immunoglobulin-like (Lig) proteins. FH binds to Lig proteins via short consensus repeat (SCR) domains 5 and 20. Competition assays suggest that FH and C4BP have distinct binding sites on Lig proteins. Moreover, FH and C4BP bound to immobilized Ligs display cofactor activity, mediating C3b and C4b degradation by FI. We demonstrated that acquisition of FH and C4BP by the LigA and LigB transformed L. biflexa have the protective role, being crucial by bacterial survival. Analysis by Cytometer fluid also confirmed the ability of L. biflexa expressing LigA and LiB to controller the deposition of C3, C4 and MAC. Lig proteins were able to bind plasminogen, which was activated to plasmin and this enzyme was able to degrade the fibrinogen, C3b and C5. These cleavages inactivate C3b and C5, preventing progression of the complement cascade and blocking the three complement pathways. (AU)

• FAPESP's process: 11/13029-1 - Interaction of Leptospire membrane proteins with human complement regulators factor H and C4BP
• Grantee: Mónica Marcela Castiblanco Valencia
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)