scholarly journals Contribution of the Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (ErpC) to Complement Resistance ofBorrelia burgdorferi

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia Hammerschmidt ◽  
Teresia Hallström ◽  
Christine Skerka ◽  
Reinhard Wallich ◽  
Brian Stevenson ◽  
...  
Keyword(s):  
Human Serum ◽  
Magnetic Beads ◽  
Surface Protein ◽  
Factor H ◽  
Surface Proteins ◽  
Complement Components ◽  
Complement Resistance ◽  
Complement Regulators ◽  
Complement Regulator ◽  
The Impact

Borrelia burgdorferievades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance ofB. burgdorferiand its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, aB. gariniistrain was generated that ectopically expresses CRASP-4. CRASP-4-producing bacteria bound CFHR1, CFHR2, and CFHR5 but not CFH. In addition, transformed spirochetes deposited significant amounts of lethal complement components on their surface and were susceptible to human serum, thus indicating that CRASP-4 plays a subordinate role in complement resistance ofB. burgdorferi.

scholarly journals Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 2 Does Not Contribute to Complement Resistance or Host Infectivity

PLoS ONE ◽  
2008 ◽  
Vol 3 (8) ◽  
pp. 3010e ◽  
Author(s):  
Adam S. Coleman ◽  
Xiuli Yang ◽  
Manish Kumar ◽  
Xinyue Zhang ◽  
Kamoltip Promnares ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Surface Protein ◽  
Complement Resistance ◽  
Complement Regulator

scholarly journals Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 1 of the Lyme Disease Spirochetes Is Expressed in Humans and Induces Antibody Responses Restricted to Nondenatured Structural Determinants

2006 ◽  
Vol 74 (12) ◽  
pp. 7024-7028 ◽  
Author(s):  
Evelyn Rossmann ◽  
Veronique Kitiratschky ◽  
Heidelore Hofmann ◽  
Peter Kraiczy ◽  
Markus M. Simon ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Surface Protein ◽  
Factor H ◽  
Antibody Responses ◽  
Dominant Factor ◽  
Serum Samples ◽  
Structural Determinants ◽  
Pathogen Persistence ◽  
Complement Regulator

ABSTRACT Borrelia burgdorferi complement regulator-acquiring surface protein 1 (CRASP-1), the dominant factor H and FHL-1-binding protein of the Lyme disease spirochete B. burgdorferi, is implicated in pathogen persistence and was recently reported to be nonimmunogenic in humans. Here we show that serum samples from Lyme disease patients contain antibodies with exclusive specificity for nondenatured structural determinants of CRASP-1.

scholarly journals Identification and Functional Characterization of Complement Regulator-Acquiring Surface Protein 1 of the Lyme Disease Spirochetes Borrelia afzelii and Borrelia garinii

2005 ◽  
Vol 73 (4) ◽  
pp. 2351-2359 ◽  
Author(s):  
Reinhard Wallich ◽  
Joseph Pattathu ◽  
Veronique Kitiratschky ◽  
Christiane Brenner ◽  
Peter F. Zipfel ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Binding Site ◽  
Binding Protein ◽  
Functional Characterization ◽  
Surface Protein ◽  
Factor H ◽  
Borrelia Garinii ◽  
Borrelia Afzelii ◽  
Complement Regulator

ABSTRACT Complement regulator-acquiring surface protein 1 (CRASP-1) is the dominant factor-H-like protein 1 (FHL-1)- and factor-H-binding protein of Borrelia burgdorferi and is suggested to contribute to persistence of the pathogen. The prototype CRASP-1 of B. burgdorferi sensu stricto (CRASP-1Bb) has been formerly characterized. As shown recently, serum-resistant Borrelia afzelii strains express a unique FHL-1 and factor H-binding protein, designated CRASP-1Ba. Here, we describe for the first time the isolation and functional characterization of the gene encoding the full-length CRASP-1Ba of 28 kDa, which, upon processing, is predicted to be 26.4 kDa. CPASP-1Ba of B. afzelii spirochetes is associated with a genetic locus encoding the orthologous gbb54 gene family that maps to the linear plasmid of approximately 54 kb. Ligand affinity blotting techniques demonstrate that both native and recombinant CRASP-1Ba molecules strongly bind to FHL-1 and much more weakly to factor H. The FHL-1 and factor-H-binding site in CRASP-1Ba is shown to be localized to a 12-amino-acid residue domain at the C terminus of the protein. For comparison, the corresponding cspA-like gene(s) of a serum-sensitive Borrelia garinii strain has also been cloned and characterized. Most notably, two CRASP-1-related B. garinii proteins were identified; however, both molecules bind only weakly to FHL-1 and not at all to factor H. The present identification of the binding site of CRASP-1Ba represents an important step forward in our understanding of the pathogenesis of Lyme disease and may be helpful to design therapeutic regimens to interfere with complement evasion strategies of human pathogenic Borrelia strains.

scholarly journals The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15

2002 ◽  
Vol 70 (10) ◽  
pp. 5604-5611 ◽  
Author(s):  
Thomas G. Duthy ◽  
Rebecca J. Ormsby ◽  
Eleni Giannakis ◽  
A. David Ogunniyi ◽  
Uwe H. Stroeher ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Regulatory System ◽  
Surface Protein ◽  
Fluid Phase ◽  
Direct Consequence ◽  
Factor H ◽  
Negative Regulator ◽  
Short Consensus Repeats ◽  
High Concentrations ◽  
Complement Regulator

ABSTRACT The innate ability of Streptococcus pneumoniae to resist complement activation and complement-mediated phagocytosis may be a direct consequence of the ability of the bacteria to bind components of the complement regulatory system. One such component, factor H (fH), is a crucial fluid-phase negative regulator of the alternative pathway of complement and is utilized by a number of pathogenic organisms to resist complement attack. The pneumococcal surface protein C (PspC [also known as CbpA] and SpsA) has been shown to bind fH, although the exact binding site within one or more of the 20 short consensus repeats (SCRs) of the molecule is not known. The purpose of the current study was to map specific SCRs on fH responsible for this binding. Initial experiments utilizing type 2 pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC mutant) showed that fH binding was PspC dependent. A purified recombinant protein derivative of PspC that lacked the proline-rich region (PspCΔPro) had a reduced binding efficiency for fH, thereby directly showing the importance of this region for the fH interaction. We have specifically shown by inhibition experiments that SCRs responsible for heparin and C3b binding of fH are not involved in binding PspC and the interaction between fH and PspC is largely hydrophobic, since no inhibition was observed in the presence of high concentrations of NaCl. Construction of SCR proteins encompassing the whole fH molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC. Further localization experiments revealed that SCR 13 and SCR 15 were required for full binding, although partial binding was retained when either SCR was removed.

Identification and characterization of a new cell surface protein possessing factor H-binding activity in the swine pathogen and zoonotic agent Streptococcus suis

2013 ◽  
Vol 62 (7) ◽  
pp. 1073-1080 ◽  
Author(s):  
Katy Vaillancourt ◽  
Laetitia Bonifait ◽  
Louis Grignon ◽  
Michel Frenette ◽  
Marcelo Gottschalk ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Protein ◽  
Streptococcus Suis ◽  
Binding Activity ◽  
Factor H ◽  
Complement Factor ◽  
Cell Surface Protein ◽  
Amino Terminal ◽  
Swine Pathogen ◽  
Complement Regulator

Streptococcus suis is a major swine pathogen and an emerging zoonotic agent. The ability of pathogenic bacteria to bind the complement regulator factor H on their cell surface may allow them to avoid complement attack and phagocytosis. The aim of this study was to characterize a new cell surface protein possessing factor H-binding activity in S. suis serotype 2. The capacity of S. suis to bind the complement regulator factor H on its surface was demonstrated by ELISA. Using a factor I–cofactor assay, it was found that the functional activity of factor H bound to S. suis was kept. Since the product of gene SSU0186 in S. suis P1/7 shared similarity with a Streptococcus pneumoniae protein (named PspC) possessing factor H-binding activity, it was proposed as a putative factor H receptor in S. suis. SSU0186 has a 1686 bp open reading frame encoding a 561 amino acid protein containing the Gram-positive cell wall anchoring motif (LPXTG) at the carboxy-terminal, an amino-terminal signal sequence, an α-helix domain, a proline-rich region and a G5 domain. The SSU0186 gene was cloned in Escherichia coli and the purified recombinant factor H-binding protein showed a molecular mass of 95 kDa, as determined by SDS-PAGE. The protein possessed the functional property of binding factor H. Sera from S. suis-infected pigs reacted with the recombinant factor H receptor, suggesting that it is produced during the course of infections. In conclusion, we identified a novel S. suis cell surface protein that binds the complement factor H. This cell surface protein may help S. suis to resist complement attack and phagocytosis and contribute to pathogenesis.

scholarly journals Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

2001 ◽  
Vol 69 (6) ◽  
pp. 3685-3691 ◽  
Author(s):  
Antti Alitalo ◽  
Taru Meri ◽  
Lasse Rämö ◽  
T. Sakari Jokiranta ◽  
Tero Heikkilä ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Human Serum ◽  
Radioligand Binding ◽  
Surface Protein ◽  
Sensu Stricto ◽  
Factor H ◽  
Factor I ◽  
Normal Human ◽  
Resistant Strains ◽  
Characteristic Features

ABSTRACT The most characteristic features of the Lyme disease pathogens, theBorrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii(n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli,Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

Staphylococcus aureus surface protein SdrE binds the complement regulator factor H to evade the immune response

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1204
Author(s):  
Julia A. Sharp ◽  
Charlene G. Echague ◽  
Pamela S. Hair ◽  
Michael D. Ward ◽  
Julius O. Nyalwidhe ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Surface Protein ◽  
Factor H ◽  
Complement Regulator

scholarly journals Borrelia burgdorferi Infection-Associated Surface Proteins ErpP, ErpA, and ErpC Bind Human Plasminogen

2008 ◽  
Vol 77 (1) ◽  
pp. 300-306 ◽  
Author(s):  
Catherine A. Brissette ◽  
Katrin Haupt ◽  
Diana Barthel ◽  
Anne E. Cooley ◽  
Amy Bowman ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Critical Role ◽  
Aminocaproic Acid ◽  
Factor H ◽  
Surface Proteins ◽  
Primary Role ◽  
Dependent Manner ◽  
Lysine Residues ◽  
Complement Regulator ◽  
Mammalian Infection

ABSTRACT Host-derived plasmin plays a critical role in mammalian infection by Borrelia burgdorferi. The Lyme disease spirochete expresses several plasminogen-binding proteins. Bound plasminogen is converted to the serine protease plasmin and thereby may facilitate the bacterium's dissemination throughout the host by degrading extracellular matrix. In this work, we demonstrate plasminogen binding by three highly similar borrelial outer surface proteins, ErpP, ErpA, and ErpC, all of which are expressed during mammalian infection. Extensive characterization of ErpP demonstrated that this protein bound in a dose-dependent manner to lysine binding site I of plasminogen. Removal of three lysine residues from the carboxy terminus of ErpP significantly reduced binding of plasminogen, and the presence of a lysine analog, ε-aminocaproic acid, inhibited the ErpP-plasminogen interaction, thus strongly pointing to a primary role for lysine residues in plasminogen binding. Ionic interactions are not required in ErpP binding of plasminogen, as addition of excess NaCl or the polyanion heparin did not have any significant effect on binding. Plasminogen bound to ErpP could be converted to the active enzyme, plasmin. The three plasminogen-binding Erp proteins can also bind the host complement regulator factor H. Plasminogen and factor H bound simultaneously and did not compete for binding to ErpP, indicating separate binding sites for both host ligands and the ability of the borrelial surface proteins to bind both host proteins.

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