Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif

PloS One
Teresia HallströmKristian Riesbeck

Abstract

Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram-positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13) bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352-374). This specific interaction leaves the terminal complement complex (TCC) regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response.

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Citations

Mar 17, 2017·Frontiers in Cellular and Infection Microbiology·Abigail I FishJuan J Martinez
Jun 29, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Silke MeinersRachel C Chambers
Jun 29, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Magnus Paulsson, Kristian Riesbeck
Mar 15, 2020·FEBS Letters·Eric S Krukonis, Joshua J Thomson
Aug 9, 2020·Frontiers in Immunology·Verena HarpfCornelia Speth
Jan 10, 2017·Frontiers in Microbiology·Elise S HovinghIlse Jongerius
May 15, 2019·International Journal of Molecular Sciences·Mónica GalochaMiguel C Teixeira
May 1, 2021·International Journal of Molecular Sciences·Christine SchlömmerMirjam Bachler

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Methods Mentioned

BETA
FCS
Assay
flow cytometry
ELISA

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