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 Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 2 (CspZ) as a Serological Marker of Human Lyme Disease

2007 ◽  
Vol 15 (3) ◽  
pp. 484-491 ◽  
Author(s):  
Peter Kraiczy ◽  
Annekatrin Seling ◽  
Catherine A. Brissette ◽  
Evelyn Rossmann ◽  
Klaus-Peter Hunfeld ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Type Strain ◽  
Surface Protein ◽  
The United States ◽  
Sensu Stricto ◽  
Serum Samples ◽  
Genes Encoding ◽  
Complement Regulator ◽  
Infecting Organisms

ABSTRACT Serological diagnosis of Lyme disease may be complicated by antigenic differences between infecting organisms and those used as test references. Accordingly, it would be helpful to include antigens whose sequences are well conserved by a broad range of Lyme disease spirochetes. In the present study, line blot analyses were performed using recombinant complement regulator-acquiring surface protein 2 (BbCRASP-2) from Borrelia burgdorferi sensu stricto strain B31 and serum samples from human Lyme disease patients from throughout the United States and Germany. The results indicated that a large proportion of the patients had produced antibodies recognizing recombinant BbCRASP-2. In addition, Lyme disease spirochetes isolated from across North America and Europe were found to contain genes encoding proteins with high degrees of similarity to the B. burgdorferi type strain B31 BbCRASP-2, consistent with the high percentage of serologically positive patients. These data indicate that BbCRASP-2 may be valuable for use in a widely effective serological assay.

scholarly journals Detection of antibodies to decorin-binding protein A (DbpA) and DbpB after infection of dogs with Borrelia burgdorferi by tick challenge

2020 ◽  
Vol 32 (3) ◽  
pp. 481-485
Author(s):  
Darby G. Oldenburg ◽  
Dean A. Jobe ◽  
Steven D. Lovrich ◽  
Rhonda L. LaFleur ◽  
Douglas W. White ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Binding Protein ◽  
Protein A ◽  
Immune Serum ◽  
Immunoglobulin M ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Serum Samples

We characterized the antibody response to decorin-binding protein A (DbpA) or DbpB from immune serum samples collected from 27 dogs infected with Borrelia burgdorferi by Ixodes scapularis ticks. Immunoglobulin M (IgM) antibodies to DbpA or DbpB were rarely detected, but high levels of IgG antibodies to DbpA were detected in 16 of 27 of the immune sera collected 1 mo after infection, 20 of 25 of the sera collected after 2 mo, and each of the 23, 17, or 11 serum samples evaluated after 3, 4, or 5 mo, respectively. In addition, IgG antibodies to DbpB were detected in 22 of 27 ( p = 0.005) tested dogs after 1 mo, and the frequency of detecting the antibodies thereafter closely mimicked the antibody responses to DbpA. Moreover, antibodies to DbpA or DbpB were not produced by dogs vaccinated with a whole-cell B. burgdorferi bacterin; removing the antibodies to DbpA by adsorption to recombinant DbpA (rDbpA) did not affect the reactivity detected by a rDbpB ELISA. Therefore, the findings from our preliminary study showed that antigenically distinct antibodies to DbpA or DbpB are produced reliably during canine infection with B. burgdorferi, and the response is not confounded by vaccination with a Lyme disease bacterin. Larger studies are warranted to more critically evaluate whether detecting the antibody responses can improve serodiagnostic confirmation of canine Lyme disease.

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 Dogs Vaccinated with Common Lyme Disease Vaccines Do Not Respond to IR6, the Conserved Immunodominant Region of the VlsE Surface Protein of Borrelia burgdorferi

2004 ◽  
Vol 11 (3) ◽  
pp. 458-462 ◽  
Author(s):  
Thomas P. O'Connor ◽  
Kathy J. Esty ◽  
Jancy L. Hanscom ◽  
Paulette Shields ◽  
Mario T. Philipp
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Controlled Trial ◽  
Animal Health ◽  
Surface Protein ◽  
Diagnostic Procedures ◽  
Immunofluorescence Assay ◽  
Serum Samples ◽  
Specific Pathogen ◽  
Fort Dodge Animal Health

ABSTRACT A 25-amino-acid synthetic peptide (C6 peptide) derived from an immunodominant conserved region (designated IR6) of the VlsE protein of Borrelia burgdorferi has been identified and used to construct immunoenzyme-based diagnostic procedures. These procedures have excellent sensitivity and specificity. Previous reports have demonstrated the usefulness of the C6 peptide as an antigen for the serodiagnosis of human and canine Lyme disease. Results indicated that assays based on the C6 peptide were nonreactive to sera from vaccinated nonexposed animals. The purpose of the present study was to confirm these results in a controlled trial by testing sera from experimentally vaccinated dogs known to be uninfected. Nine specific-pathogen-free beagles were assigned to one of three vaccine groups, each containing three dogs. Each group received one of three commercial Lyme vaccines: RECOMBITEK Lyme (Merial), LymeVax (Fort Dodge Animal Health), and Galaxy Lyme (Schering-Plough Animal Health). Each animal was administered a total of five doses of vaccine over a period of 39 weeks. Serum samples were collected prior to vaccination and then on a weekly basis from weeks 3 to 18 and from weeks 33 to 43. Selected samples were tested by the immunofluorescence assay (IFA) and the Western blot (WB) assay using whole-cell B. burgdorferi antigen extracts, and the results were compared to those obtained with two immunoenzyme-based procedures formatted by using the C6 peptide. Serum specimens from all animals were reactive to the IFA and WB assay at week 5 and became highly reactive following the administration of multiple doses of vaccine. All serum specimens were uniformly nonreactive in the C6 peptide immunoenzyme procedures at all time points throughout the study.

scholarly journals LuxS-Mediated Quorum Sensing in Borrelia burgdorferi, the Lyme Disease Spirochete

2002 ◽  
Vol 70 (8) ◽  
pp. 4099-4105 ◽  
Author(s):  
Brian Stevenson ◽  
Kelly Babb
Keyword(s):  
Lyme Disease ◽  
Quorum Sensing ◽  
Borrelia Burgdorferi ◽  
Cell Communication ◽  
Factor H ◽  
Autoinducer 2 ◽  
Specific Proteins ◽  
Complement Regulator ◽  
Regulate Protein ◽  
Infection Processes

ABSTRACT The establishment of Borrelia burgdorferi infection involves numerous interactions between the bacteria and a variety of vertebrate host and arthropod vector tissues. This complex process requires regulated synthesis of many bacterial proteins. We now demonstrate that these spirochetes utilize a LuxS/autoinducer-2 (AI-2)-based quorum-sensing mechanism to regulate protein expression, the first system of cell-cell communication to be described in a spirochete. The luxS gene of B. burgdorferi was identified and demonstrated to encode a functional enzyme by complementation of an Escherichia coli luxS mutant. Cultured B. burgdorferi responded to AI-2 by altering the expression levels of a large number of proteins, including the complement regulator factor H-binding Erp proteins. Through this mechanism, a population of Lyme disease spirochetes may synchronize production of specific proteins needed for infection processes.

The complement regulator-acquiring surface protein 3 of the Lyme disease spirochete Borrelia spielmanii interacts with distinct members of the factor H protein family

2009 ◽  
Vol 46 (14) ◽  
pp. 2834
Author(s):  
Peter Kraiczy ◽  
Annekatrin Seling ◽  
Volker Fingerle ◽  
Christine Skerka ◽  
Reinhard Wallich ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Surface Protein ◽  
Protein Family ◽  
Factor H ◽  
Complement Regulator ◽  
H Protein

scholarly journals Characterization of Unique Regions of Borrelia burgdorferi Surface-Located Membrane Protein 1

2010 ◽  
Vol 78 (11) ◽  
pp. 4477-4487 ◽  
Author(s):  
Xiuli Yang ◽  
Tiffany R. Lenhart ◽  
Toru Kariu ◽  
Juan Anguita ◽  
Darrin R. Akins ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Membrane Protein ◽  
Borrelia Burgdorferi ◽  
Surface Protein ◽  
Integral Membrane Protein ◽  
Terminal Region ◽  
Pathogen Persistence ◽  
Bactericidal Effects ◽  
Organ Specific

ABSTRACT The pathogen of Lyme disease, Borrelia burgdorferi, produces a putative surface protein termed “surface-located membrane protein 1” (Lmp1). Lmp1 has been shown previously to assist the microbe in evasion of host-acquired immune defenses and in the establishment of persistent infection of mammals. Here, we show that Lmp1 is an integral membrane protein with surface-exposed N-terminal, middle, and C-terminal regions. During murine infection, antibodies recognizing these three protein regions were produced. Separate immunization of mice with each of the discrete regions exerted differential effects on spirochete survival during infection. Notably, antibodies against the C-terminal region primarily interfered with B. burgdorferi persistence in the joints, while antibodies specific to the N-terminal region predominantly affected pathogen levels in the heart, including the development of carditis. Genetic reconstitution of lmp1 deletion mutants with the lmp1 N-terminal region significantly enhanced its ability to resist the bactericidal effects of immune sera and also was observed to increase pathogen survival in vivo. Taken together, the combined data suggest that the N-terminal region of Lmp1 plays a distinct role in spirochete survival and other parts of the protein are related to specific functions corresponding to pathogen persistence and tropism during infection that is displayed in an organ-specific manner. The findings reported here underscore the fact that surface-exposed regions of Lmp1 could potentially serve as vaccine targets or antigenic regions that could alter the course of natural Lyme disease.

scholarly journals Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C6 Test for Lyme Disease

2006 ◽  
Vol 14 (1) ◽  
pp. 90-93 ◽  
Author(s):  
Monica E. Embers ◽  
Gary P. Wormser ◽  
Ira Schwartz ◽  
Dale S. Martin ◽  
Mario T. Philipp
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Antibody Responses ◽  
Antibody Detection ◽  
23S Rrna ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Altered Expression ◽  
Genetic Region ◽  
Length Polymorphisms

ABSTRACT Detection of antibody to C6, a peptide that reproduces the sequence of the sixth invariable region within the central domain of the VlsE protein of Borrelia burgdorferi, is used currently for the serologic diagnosis of Lyme disease in humans. B. burgdorferi isolates taken from infected humans can be categorized into specific genetic subtypes (designated RST1, -2, and -3) by restriction fragment length polymorphisms in the 16S to 23S rRNA spacer sequence. Many of these, usually categorized as RST2, retain only segments of the linear plasmid lp28-1, which encodes VlsE. The VlsE genetic region is retained, but altered expression of this molecule could affect diagnosis by the C6 enzyme-linked immunosorbent assay (ELISA). Serum samples from patients infected with each of the three genotypes and from mice infected with three RST2 isolates were tested with the C6 ELISA. Such isolates elicited marked C6 responses in infected mice. The sensitivity of C6 antibody detection in patients infected with RST2 spirochetes was statistically indistinguishable from detection of RST1 and RST3 infections. These findings demonstrate that diagnosis by C6 ELISA remains effective for infection with all B. burgdorferi genotypes, including those with incomplete lp28-1 plasmids.

scholarly journals Borrelia burgdorferi Regulates Expression of Complement Regulator-Acquiring Surface Protein 1 during the Mammal-Tick Infection Cycle

2005 ◽  
Vol 73 (11) ◽  
pp. 7398-7405 ◽  
Author(s):  
Kate von Lackum ◽  
Jennifer C. Miller ◽  
Tomasz Bykowski ◽  
Sean P. Riley ◽  
Michael E. Woodman ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Immune Evasion ◽  
Expression Patterns ◽  
Surface Protein ◽  
Factor H ◽  
Complement Factor ◽  
Human Pathogens ◽  
Infection Cycle ◽  
Tick Infection ◽  
Complement Regulator

ABSTRACT During the natural mammal-tick infection cycle, the Lyme disease spirochete Borrelia burgdorferi comes into contact with components of the alternative complement pathway. B. burgdorferi, like many other human pathogens, has evolved the immune evasion strategy of binding two host-derived fluid-phase regulators of complement, factor H and factor H-like protein 1 (FHL-1). The borrelial complement regulator-acquiring surface protein 1 (CRASP-1) is a surface-exposed lipoprotein that binds both factor H and FHL-1. Analysis of CRASP-1 expression during the mammal-tick infectious cycle indicated that B. burgdorferi expresses this protein during mammalian infection, supporting the hypothesized role for CRASP-1 in immune evasion. However, CRASP-1 synthesis was repressed in bacteria during colonization of vector ticks. Analysis of cultured bacteria indicated that CRASP-1 is differentially expressed in response to changes in pH. Comparisons of CRASP-1 expression patterns with those of other infection-associated B. burgdorferi proteins, including the OspC, OspA, and Erp proteins, indicated that each protein is regulated through a unique mechanism.

Sign in / Sign up

Export Citation Format

Share Document