论文信息 - Mechanism of Borrelia immune evasion by FhbA-related proteins

Mechanism of Borrelia immune evasion by FhbA-related proteins

Immune evasion facilitates survival of Borrelia, leading to infections like relapsing fever and Lyme disease. Important mechanism for complement evasion is acquisition of the main host complement inhibitor, factor H (FH). By determining the 2.2 Å crystal structure of Factor H binding protein A (FhbA) from Borrelia hermsii in complex with FH domains 19–20, combined with extensive mutagenesis, we identified the structural mechanism by which B. hermsii utilizes FhbA in immune evasion. Moreover, structure-guided sequence database analysis identified a new family of FhbA-related immune evasion molecules from Lyme disease and relapsing fever Borrelia. Conserved FH-binding mechanism within the FhbA-family was verified by analysis of a novel FH-binding protein from B. duttonii. By sequence analysis, we were able to group FH-binding proteins of Borrelia into four distinct phyletic types and identified novel putative FH-binding proteins. The conserved FH-binding mechanism of the FhbA-related proteins could aid in developing new approaches to inhibit virulence and complement resistance in Borrelia.

[1] M. Józsi,et al. Regulation of regulators: Role of the complement factor H-related proteins. , 2019, Seminars in immunology.

[2] M. Ramonienė,et al. Comparison , 2019, Encyclopedia of Biometrics.

[3] B. Garcia,et al. Structural determination of the complement inhibitory domain of Borrelia burgdorferi BBK32 provides insight into classical pathway complement evasion by Lyme disease spirochetes , 2019, PLoS pathogens.

[4] R. Wubbolts,et al. Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specific antibiotics , 2019, Scientific Reports.

[5] Alexander W. Gofton,et al. The genus Borrelia reloaded , 2018, PloS one.

[6] Torsten Schwede,et al. SWISS-MODEL: homology modelling of protein structures and complexes , 2018, Nucleic Acids Res..

[7] F. Strle,et al. Lyme borreliosis-from tick bite to diagnosis and treatment. , 2018, FEMS microbiology reviews.

[8] A. Goldman,et al. Crystal structure of a tripartite complex between C3dg, C-terminal domains of factor H and OspE of Borrelia burgdorferi , 2017, PloS one.

[9] J. Coburn,et al. Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival , 2017, Cellular microbiology.

[10] P. Zipfel,et al. Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties , 2017, Scientific Reports.

[11] Ashley L. Marcinkiewicz,et al. There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes , 2017, Front. Microbiol..

[12] Simon J. Clark,et al. Complement factor H in host defense and immune evasion , 2016, Cellular and Molecular Life Sciences.

[13] M. N. Garcia,et al. Tick-Borne Relapsing Fever Spirochetes in the Americas , 2016, Veterinary sciences.

[14] S. Meri,et al. Disturbed sialic acid recognition on endothelial cells and platelets in complement attack causes atypical hemolytic uremic syndrome. , 2016, Blood.

[15] Liisa Holm,et al. Dali server update , 2016, Nucleic Acids Res..

[16] B. Garcia,et al. Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex , 2016, PLoS pathogens.

[17] P. Zipfel,et al. BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by inhibiting assembly of the membrane attack complex , 2016, Molecular microbiology.

[18] S. Cutler,et al. Relapsing Fever Borreliae : A Global Review , 2015 .

[19] M. Varjosalo,et al. Complement Factor H Binds to Human Serum Apolipoprotein E and Mediates Complement Regulation on High Density Lipoprotein Particles* , 2015, The Journal of Biological Chemistry.

[20] V. Frémeaux-Bacchi,et al. Complement System Part I – Molecular Mechanisms of Activation and Regulation , 2015, Front. Immunol..

[21] S. Rodríguez de Córdoba,et al. Factor H-related proteins determine complement-activating surfaces. , 2015, Trends in immunology.

[22] Michael J E Sternberg,et al. The Phyre2 web portal for protein modeling, prediction and analysis , 2015, Nature Protocols.

[23] I. Akopjana,et al. Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H. , 2015, Biochimica et biophysica acta.

[24] A. Kazaks,et al. Structural characterization of CspZ, a complement regulator factor H and FHL‐1 binding protein from Borrelia burgdorferi , 2014, The FEBS journal.

[25] R. Marconi,et al. The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro , 2014, Infection and Immunity.

[26] F. Cabello,et al. Borrelia chilensis, a new member of the Borrelia burgdorferi sensu lato complex that extends the range of this genospecies in the Southern Hemisphere. , 2014, Environmental microbiology.

[27] D. Aucoin,et al. Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever , 2014, Infection and Immunity.

[28] M. Drancourt,et al. Relapsing fever borreliae in Africa. , 2013, The American journal of tropical medicine and hygiene.

[29] A. Kazaks,et al. Structure of an outer surface lipoprotein BBA64 from the Lyme disease agent Borrelia burgdorferi which is critical to ensure infection after a tick bite. , 2013, Acta crystallographica. Section D, Biological crystallography.

[30] A. Goldman,et al. Structural Basis for Complement Evasion by Lyme Disease Pathogen Borrelia burgdorferi , 2013, The Journal of Biological Chemistry.

[31] A. Goldman,et al. Microbes Bind Complement Inhibitor Factor H via a Common Site , 2013, PLoS pathogens.

[32] G. Larsson,et al. A dual tag system for facilitated detection of surface expressed proteins in Escherichia coli , 2012, Microbial Cell Factories.

[33] D. Radune,et al. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids , 2012, PloS one.

[34] H. Rohde,et al. Staphylococcus epidermidis polysaccharide intercellular adhesin activates complement. , 2011, FEMS immunology and medical microbiology.

[35] M. Neteler,et al. Lyme borreliosis in Europe. , 2011, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[36] A. Goldman,et al. Dual interaction of factor H with C3d and glycosaminoglycans in host–nonhost discrimination by complement , 2011, Proceedings of the National Academy of Sciences.

[37] M. Schott,et al. Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis , 2010, PLoS neglected tropical diseases.

[38] M. Schott,et al. Molecular Characterization of the Interaction of Borrelia parkeri and Borrelia turicatae with Human Complement Regulators , 2010, Infection and Immunity.

[39] John D Lambris,et al. Structure of C3b-factor H and implications for host protection by complement regulators , 2009, Nature Immunology.

[40] R. Marconi,et al. Identification of an Antiparallel Coiled-Coil/Loop Domain Required for Ligand Binding by the Borrelia hermsii FhbA Protein: Additional Evidence for the Role of FhbA in the Host-Pathogen Interaction , 2008, Infection and Immunity.

[41] K. Henrick,et al. Inference of macromolecular assemblies from crystalline state. , 2007, Journal of molecular biology.

[42] R. Marconi,et al. Delineation of Species-Specific Binding Properties of the CspZ Protein (BBH06) of Lyme Disease Spirochetes: Evidence for New Contributions to the Pathogenesis of Borrelia spp , 2007, Infection and Immunity.

[43] P. Zipfel,et al. Dual Binding Specificity of a Borrelia hermsii-Associated Complement Regulator-Acquiring Surface Protein for Factor H and Plasminogen Discloses a Putative Virulence Factor of Relapsing Fever Spirochetes12 , 2007, The Journal of Immunology.

[44] S. Rebaudet,et al. Epidemiology of relapsing fever borreliosis in Europe. , 2006, FEMS immunology and medical microbiology.

[45] Sonia Bahlani,et al. Immunological and Molecular Analyses of the Borrelia hermsii Factor H and Factor H-Like Protein 1 Binding Protein, FhbA: Demonstration of Its Utility as a Diagnostic Marker and Epidemiological Tool for Tick-Borne Relapsing Fever , 2006, Infection and Immunity.

[46] A. Blom,et al. Relapsing Fever Spirochetes Borrelia recurrentis and B. duttonii Acquire Complement Regulators C4b-Binding Protein and Factor H , 2006, Infection and Immunity.

[47] A. Goldman,et al. Structure of complement factor H carboxyl‐terminus reveals molecular basis of atypical haemolytic uremic syndrome , 2006, The EMBO journal.