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.

scholarly journals Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

2008 ◽  
Vol 298 ◽  
pp. 249-256 ◽  
Author(s):  
Tomasz Bykowski ◽  
Michael E. Woodman ◽  
Anne E. Cooley ◽  
Catherine A. Brissette ◽  
Reinhard Wallich ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Expression Patterns ◽  
Surface Proteins ◽  
Infection Cycle ◽  
Tick Infection ◽  
Complement Regulator

scholarly journals Coordinated Expression of Borrelia burgdorferi Complement Regulator-Acquiring Surface Proteins during the Lyme Disease Spirochete's Mammal-Tick Infection Cycle

2007 ◽  
Vol 75 (9) ◽  
pp. 4227-4236 ◽  
Author(s):  
Tomasz Bykowski ◽  
Michael E. Woodman ◽  
Anne E. Cooley ◽  
Catherine A. Brissette ◽  
Volker Brade ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Expression Patterns ◽  
Resistance Mechanism ◽  
Factor H ◽  
Surface Proteins ◽  
Mrna Levels ◽  
Tick Infection ◽  
Complement Regulator ◽  
Mammalian Infection

ABSTRACT The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts’ alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three closely related proteins, BbCRASP-3, -4, and -5, encoded by erpP, erpC, and erpA, respectively. We now present analyses of the recently identified BbCRASP-2 and cspZ expression patterns throughout the B. burgdorferi infectious cycle, plus novel analyses of BbCRASP-1 and erp-encoded BbCRASPs. Our results, combined with data from earlier studies, indicate that BbCRASP-2 is produced primarily during established mammalian infection, while BbCRASP-1 is produced during tick-to-mammal and mammal-to-tick transmission stages but not during established mammalian infection, and Erp-BbCRASPs are produced from the time of transmission from infected ticks into mammals until they are later acquired by other feeding ticks. Transcription of cspZ and synthesis of BbCRASP-2 were severely repressed during cultivation in laboratory medium relative to mRNA levels observed during mammalian infection, and cspZ expression was influenced by culture temperature and pH, observations which will assist identification of the mechanisms employed by B. burgdorferi to control expression of this borrelial infection-associated protein.

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.

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 Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection

2006 ◽  
Vol 74 (6) ◽  
pp. 3554-3564 ◽  
Author(s):  
Kit Tilly ◽  
Jonathan G. Krum ◽  
Aaron Bestor ◽  
Mollie W. Jewett ◽  
Dorothee Grimm ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Salivary Glands ◽  
Early Stage ◽  
Natural Infection ◽  
Surface Protein ◽  
Mammalian Host ◽  
Infection Cycle ◽  
Persistently Infected ◽  
Tick Infection ◽  
Mammalian Infection

ABSTRACT This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an ospC mutant complemented with an unstable copy of the ospC gene and show that B. burgdorferi's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented ospC mutant strain no longer carried the wild-type copy of ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these ospC mutant spirochetes did not infect naive mice. ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick infection cycle.

scholarly journals Staphylococcus aureus Surface Protein SdrE Binds Complement Regulator Factor H as an Immune Evasion Tactic

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e38407 ◽  
Author(s):  
Julia A. Sharp ◽  
Charlene G. Echague ◽  
Pamela S. Hair ◽  
Michael D. Ward ◽  
Julius O. Nyalwidhe ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Surface Protein ◽  
Factor H ◽  
Complement Regulator

scholarly journals Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel ‘close, dock, lock and latch' mechanism for complement evasion

2017 ◽  
Vol 474 (10) ◽  
pp. 1619-1631 ◽  
Author(s):  
Yingjie Zhang ◽  
Minhao Wu ◽  
Tianrong Hang ◽  
Chengliang Wang ◽  
Ye Yang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Alternative Pathway ◽  
Regulatory Protein ◽  
Surface Protein ◽  
Factor H ◽  
Host Cells ◽  
Main Body ◽  
Complement Factor ◽  
C Terminus

Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine–aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE–CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206–1226), which binds SdrE N2 and N3 domains (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3 and the SdrEN2N3–CFH1206–1226 complex. Comparison of the structure of the CFH–SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrEN2N3 adopts a ‘close’ state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel ‘close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a ‘clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion.

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
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