Differential Binding of Host Complement Inhibitor Factor H by<i>Borrelia burgdorferi</i>Erp Surface Proteins: a Possible Mechanism Underlying the Expansive Host Range of Lyme Disease Spirochetes

Stevenson, Brian; El‐Hage, Nazira; Hines, Melissa A.; Miller, Jennifer C.; Babb, Kelly

doi:10.1128/iai.70.2.491-497.2002

Cited by 206 publications

(184 citation statements)

References 72 publications

(76 reference statements)

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“…29 Two type of proteins that may be involved in complement resistance in B. burgdorferi have been reported. One of them is OspE/Erp proteins that bind factor H. 30,31 More recently, a CD59-like molecule that inhibits the assembly of MAC was described on the outer membrane of B. burgdorferi. 32 We found deposition of MAC in the heart of IS-NHPs not only on spirochetes but also on the membranes of cardiac myocytes.…”

Section: Discussionmentioning

confidence: 99%

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Cadavid

Bai

Hodzic

et al. 2004

Laboratory Investigation

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To investigate cardiac involvement in the non-human primate (NHP) model of Lyme disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu stricto strains N40 (BbN40) by needle (N ¼ 22, 14 immunocompetent (IC), seven permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP)) or by tick-bite (N ¼ 4, all TISP) or strain 297 (Bb297) by needle (N ¼ 2 IS), or with B. garinii strains Pbi (N ¼ 4, 2 TISP and 2 IS), 793 (N ¼ 2, TISP) or Pli (N ¼ 2, TISP). Five uninfected NHPs were used as controls. Infection and inflammation was studied in the hearts and the aorta removed at necropsy 2-32 months after inoculation by (1) H&E and trichrome-staining; (2) immunohistochemistry and digital image analysis; (3) Western blot densitometry; and (4) TaqMan RT-PCR. All NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The predominant cells were T cells, plasma cells, and macrophages. There was increased IgG and IgM in the heart independent of immunosuppression. The B-cell chemokine BLC was significantly increased in IS-NHPs. There was increased deposition of the complement membrane attack complex (MAC) in TISP and IS-NHPs. The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis in NHPs infected with B. burgdorferi is frequent and can persist for years but is mild unless they are immunosupressed.

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Section: Discussionmentioning

confidence: 99%

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Cadavid

Bai

Hodzic

et al. 2004

Laboratory Investigation

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“…It has been proposed that amino acid sequence differences of some proteins between strains influence the efficiency of bacteria for infection of different host species . As one example, sequence differences among Erp proteins alter their ability to bind complement factor H, which is thought to contribute to the host range of Lyme disease borreliae (Kraiczy et al, 2001b;Kurtenbach et al, 2002a, b;Stevenson et al, 2002). Perhaps EppA proteins also interact with host proteins that differ in sequence between diverse hosts in nature?…”

Section: B Burgdorferi Eppa Genesmentioning

confidence: 99%

“…The cp32 plasmids are largely identical to each other and vary significantly at only a few loci, one of which is the erp locus. The encoded Erp proteins are surface-exposed lipoproteins that are produced during mammalian infection and bind to complement regulatory factor H, apparently contributing to the resistance of these bacteria to host complementmediated killing (Alitalo et al, 2002;Hellwage et al, 2001;Kraiczy et al, 2001a;Kurtenbach et al, 2002a;Stevenson et al, 2002). One of the first erp loci to be identified, the pG gene of B. burgdorferi strain ZS7, contains an unrelated downstream gene named bapA (Wallich et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Immunological and genetic characterization of Borrelia burgdorferi BapA and EppA proteins

Miller

Stevenson

2003

Microbiology

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A large majority of examined Lyme disease spirochaete isolates were demonstrated to contain one or both of the paralogous genes bapA and eppA. Immunological analyses of serum samples collected from infected patients coupled with comparative sequence analyses indicated that bapA gene sequences are quite stable but the encoded proteins do not provoke a strong immune response in most individuals. Conversely, EppA proteins are much more antigenic but vary widely in sequence between different bacteria. Considerable evidence of insertion, deletion and other mutations within eppA genes was observed. A number of significant recombination events were also found to have occurred in regions flanking bapA genes, while the genes themselves rarely exhibited evidence of mutation, suggesting strong selective pressure to maintain BapA sequences within narrow limits. Data from these and other studies suggest important roles for BapA and EppA during the Borrelia burgdorferi infectious cycle.

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“…produces several different outer surface proteins collectively termed CRASPs (complement regulator-acquiring surface proteins). These lipoproteins share affinities for the host fluid phase negative regulators of complement factor H and/or FHL-1 (factor H-like protein 1) (Hellwage et al, 2001;Kraiczy et al, 2001Kraiczy et al, , 2003Kraiczy et al, , 2004aKraiczy et al, , 2004bAlitalo et al, 2002Alitalo et al, , 2005Stevenson et al, 2002;McDowell et al, 2003;Hartmann et al, 2006;Kraiczy and Würzner, 2006;Herzberger et al, 2007). Those two host proteins promote breakdown of C3b and inactivation of the alternative pathway C3 convertase (Janeway et al, 1999;Kraiczy and Würzner, 2006).…”

Section: Introductionmentioning

confidence: 99%

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

Bykowski

Woodman

Cooley

et al. 2008

International Journal of Medical Microbiology

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Host complement is widely distributed throughout mammalian body fluids and can be activated immediately as part of the first line of defense against invading pathogens. The agent of Lyme disease, Borrelia burgdorferi sensu lato (s.l.), is naturally resistant to that innate immune defense system of its hosts. One resistance mechanism appears to involve binding fluid-phase regulators of complement to distinct borrelial outer surface molecules known as CRASPs (complement regulator acquiring surface proteins). Using sensitive molecular biology techniques, expression patterns of all three classes of genes encoding the CRASPs of B. burgdorferi sensu stricto (BbCRASPs) have been analyzed throughout the natural tick-mammal infection cycle. Each class shows a different expression profile in vivo and the results are summarized herein. Studies on the expression of B. burgdorferi genes using animal models of infection have advanced our knowledge on the ability of the causative agent to circumvent innate immune defenses, the contributions of CRASPs to spirochete infectivity, and the pathogenesis of Lyme disease.

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Differential Binding of Host Complement Inhibitor Factor H byBorrelia burgdorferiErp Surface Proteins: a Possible Mechanism Underlying the Expansive Host Range of Lyme Disease Spirochetes

Cited by 206 publications

References 72 publications

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Immunological and genetic characterization of Borrelia burgdorferi BapA and EppA proteins

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

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