Mapping the Ligand-Binding Region of Borrelia hermsii Fibronectin-Binding Protein

Brenner, Christiane; Bomans, Katharina; Habicht, Jüri; Simon, Markus M.; Wallich, Reinhard

doi:10.1371/journal.pone.0063437

Cited by 8 publications

(28 citation statements)

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“…The binding affinities of human and bovine fibronectin for recombinant BHA007 of ϳ20 to 30 nM were comparable to those for fibronectin-binding proteins in Gram-positive cocci, including F2 of Streptococcus pyogenes and FnBPA of Staphylococcus aureus (56-59). Brenner et al reported that BHA007 and its orthologs in B. turicatae and B. parkeri bound to fibronectin but neither C4b-binding protein nor C1 esterase inhibitor (60). They mapped the ligand-binding site for the B. hermsii protein by using blotting assays with human fibronectin in serum and RF Borrelia fibronectin-binding protein deletion mutants and made use of a spontaneous mutant of bha007 that encoded a polypeptide lacking the C-terminal half of BHA007 (60).…”

Section: Discussionmentioning

confidence: 99%

“…Brenner et al reported that BHA007 and its orthologs in B. turicatae and B. parkeri bound to fibronectin but neither C4b-binding protein nor C1 esterase inhibitor (60). They mapped the ligand-binding site for the B. hermsii protein by using blotting assays with human fibronectin in serum and RF Borrelia fibronectin-binding protein deletion mutants and made use of a spontaneous mutant of bha007 that encoded a polypeptide lacking the C-terminal half of BHA007 (60). Depending on the RF Borrelia species, the fibronectin-binding domains within these proteins were mapped somewhere between amino acid positions 180 and 230 in the unprocessed polypeptides with the signal peptides (60).…”

Section: Discussionmentioning

confidence: 99%

“…They mapped the ligand-binding site for the B. hermsii protein by using blotting assays with human fibronectin in serum and RF Borrelia fibronectin-binding protein deletion mutants and made use of a spontaneous mutant of bha007 that encoded a polypeptide lacking the C-terminal half of BHA007 (60). Depending on the RF Borrelia species, the fibronectin-binding domains within these proteins were mapped somewhere between amino acid positions 180 and 230 in the unprocessed polypeptides with the signal peptides (60). As for the protein that those authors identified in strain HS1 of B. hermsii, its protein was truncated at 191 residues and did not contain a predicted fibronectin-binding domain.…”

Section: Discussionmentioning

confidence: 99%

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Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

et al. 2014

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To identify and characterize surface proteins expressed by the relapsing fever (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of in situ protease susceptibility and agglutination of Vtp ؊ cells by anti-BHA007 antibodies, and was not essential for in vitro growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with K d (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in Borrelia species that bind to fibronectin as well as other host proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

et al. 2014

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“…bind human and various animal C4BP (143, 148, 149, 157, 158). A comprehensive analysis identified outer surface proteins (Osps) associated with C4BP including OspA, Vlps, variable membrane proteins (Vmps), and several unidentified Osps (159).…”

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

Stone

Brissette

2017

Front. Immunol.

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The emerging pathogen, Borrelia miyamotoi, is a relapsing fever spirochete vectored by the same species of Ixodes ticks that carry the causative agents of Lyme disease in the US, Europe, and Asia. Symptoms caused by infection with B. miyamotoi are similar to a relapsing fever infection. However, B. miyamotoi has adapted to different vectors and reservoirs, which could result in unique physiology, including immune evasion mechanisms. Lyme Borrelia utilize a combination of Ixodes-produced inhibitors and native proteins [i.e., factor H-binding proteins (FHBPs)/complement regulator-acquiring surface proteins, p43, BBK32, BGA66, BGA71, CD59-like protein] to inhibit complement, while some relapsing fever spirochetes use C4b-binding protein and likely Ornithodoros-produced inhibitors. To evade the humoral response, Borrelia utilize antigenic variation of either outer surface proteins (Osps) and the Vmp-like sequences (Vls) system (Lyme borreliae) or variable membrane proteins (Vmps, relapsing fever borreliae). B. miyamotoi possesses putative FHBPs and antigenic variation of Vmps has been demonstrated. This review summarizes and compares the common mechanisms utilized by Lyme and relapsing fever spirochetes, as well as the current state of understanding immune evasion by B. miyamotoi.

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“…However, as the binding of these components or regulators to borrelial proteins occurs on the spirochete surface, lysing the cells prior to incubation may change the structure of borrelial proteins and prevent binding. This may explain some inconsistent results when analyzing the complement regulator-binding activity of borreliae using this method (Table 1 ; Hartmann et al, 2006 ; McDowell et al, 2006 ; Rogers and Marconi, 2007 ; Bhide et al, 2009 ; Grosskinsky et al, 2010 ; Brenner et al, 2013 ).…”

Section: Approaches To Study Mechanisms Of Serum Resistance Factors Imentioning

confidence: 99%

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes

2017

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Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae, the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae, carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms of Borrelia spp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme disease borreliae that can be applied to relapsing fever borreliae. Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.

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Mapping the Ligand-Binding Region of Borrelia hermsii Fibronectin-Binding Protein

Cited by 8 publications

References 50 publications

Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

Fibronectin-Binding Protein of Borrelia hermsii Expressed in the Blood of Mice with Relapsing Fever

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes

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