BGA66 and BGA71 facilitate complement resistance of <i>Borrelia bavariensis</i> by inhibiting assembly of the membrane attack complex

Hammerschmidt, Claudia; Klevenhaus, Yvonne; Koenigs, Arno; Hallström, Teresia; Fingerle, Volker; Skerka, Christine; Pos, Klaas M.; Zipfel, Peter F.; Wallich, Reinhard; Kraiczy, Peter

doi:10.1111/mmi.13239

Cited by 52 publications

(78 citation statements)

References 79 publications

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“…1A). As expected, binding of FH could also be detected with BpcA, HcpA, and CspA, while BtcA and BGA71 served as negative controls and did not bind FH 26, 29 . In addition, Far Western blotting was conducted as an independent approach to confirm interaction of the recombinant proteins with FH.…”

Section: Resultssupporting

confidence: 70%

“…To investigate differences in the complement-binding capabilities between the putative FH-binding protein of B. miyamotoi and additional homologous complement-interacting proteins from tick-borne and louse-borne relapsing fever spirochetes, e.g. B. parkeri (BpcA), B. turicatae (BtcA), and B. recurrentis (HcpA) a comparative analysis was performed 20, 26, 29, 30 (Supplementary Figure S1). CspA from the Lyme disease spirochetes B. burgdorferi and BGA71 from B. bavariensis were included as additional controls 29, 31, 32 .…”

Section: Resultsmentioning

confidence: 99%

“…B. parkeri (BpcA), B. turicatae (BtcA), and B. recurrentis (HcpA) a comparative analysis was performed 20, 26, 29, 30 (Supplementary Figure S1). CspA from the Lyme disease spirochetes B. burgdorferi and BGA71 from B. bavariensis were included as additional controls 29, 31, 32 . All proteins were produced with a N-terminal His 6 -tag and purified via Ni-NTA affinity chromatography.…”

Section: Resultsmentioning

confidence: 99%

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Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

Röttgerding

Wagemakers

Koetsveld

et al. 2017

Sci Rep

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Borrelia (B.) miyamotoi, an emerging tick-borne relapsing fever spirochete, resists complement-mediated killing. To decipher the molecular principles of immune evasion, we sought to identify determinants contributing to complement resistance. Employing bioinformatics, we identified a gene encoding for a putative Factor H-binding protein, termed CbiA (complement binding and inhibitory protein A). Functional analyses revealed that CbiA interacted with complement regulator Factor H (FH), C3, C3b, C4b, C5, and C9. Upon binding to CbiA, FH retained its cofactor activity for Factor I-mediated inactivation of C3b. The Factor H-binding site within CbiA was mapped to domain 20 whereby the C-terminus of CbiA was involved in FH binding. Additionally, CbiA directly inhibited the activation of the classical pathway and the assembly of the terminal complement complex. Of importance, CbiA displayed inhibitory activity when ectopically produced in serum-sensitive B. garinii G1, rendering this surrogate strain resistant to human serum. In addition, long-term in vitro cultivation lead to an incremental loss of the cbiA gene accompanied by an increase in serum susceptibility. In conclusion, our data revealed a dual strategy of B. miyamotoi to efficiently evade complement via CbiA, which possesses complement binding and inhibitory activities.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

Röttgerding

Wagemakers

Koetsveld

et al. 2017

Sci Rep

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“…Outer surface lipoproteins important for tissue colonization (DbpA, BBK_32) and evasion of complement-dependent killing (CRASPs) have been linked to tropism and/or pathogenic differences [38, 54–57]. In the B .…”

Section: Discussionmentioning

confidence: 99%

Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii

et al. 2016

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Borrelia mayonii, a Borrelia burgdorferi sensu lato (Bbsl) genospecies, was recently identified as a cause of Lyme borreliosis (LB) among patients from the upper midwestern United States. By microscopy and PCR, spirochete/genome loads in infected patients were estimated at 105 to 106 per milliliter of blood. Here, we present the full chromosome and plasmid sequences of two B. mayonii isolates, MN14-1420 and MN14-1539, cultured from blood of two of these patients. Whole genome sequencing and assembly was conducted using PacBio long read sequencing (Pacific Biosciences RSII instrument) followed by hierarchical genome-assembly process (HGAP). The B. mayonii genome is ~1.31 Mbp in size (26.9% average GC content) and is comprised of a linear chromosome, 8 linear and 7 circular plasmids. Consistent with its taxonomic designation as a new Bbsl genospecies, the B. mayonii linear chromosome shares only 93.83% average nucleotide identity with other genospecies. Both B. mayonii genomes contain plasmids similar to B. burgdorferi sensu stricto lp54, lp36, lp28-3, lp28-4, lp25, lp17, lp5, 5 cp32s, cp26, and cp9. The vls locus present on lp28-10 of B. mayonii MN14-1420 is remarkably long, being comprised of 24 silent vls cassettes. Genetic differences between the two B. mayonii genomes are limited and include 15 single nucleotide variations as well as 7 fewer silent vls cassettes and a lack of the lp5 plasmid in MN14-1539. Notably, 68 homologs to proteins present in B. burgdorferi sensu stricto appear to be lacking from the B. mayonii genomes. These include the complement inhibitor, CspZ (BB_H06), the fibronectin binding protein, BB_K32, as well as multiple lipoproteins and proteins of unknown function. This study shows the utility of long read sequencing for full genome assembly of Bbsl genomes, identifies putative genome regions of B. mayonii that may be linked to clinical manifestation or tissue tropism, and provides a valuable resource for pathogenicity, diagnostic and vaccine studies.

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“…A comprehensive analysis identified outer surface proteins (Osps) associated with C4BP including OspA, Vlps, variable membrane proteins (Vmps), and several unidentified Osps (159). However, other studies have observed no binding of C4BP by Borrelia spp (143, 150, 160). These contradictory data may be due to differences in experimental design including the use of different strains, growth medium, temperatures, growth phases, and the use of recombinant versus native human C4BP.…”

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 78%

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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BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by inhibiting assembly of the membrane attack complex

Cited by 52 publications

References 79 publications

Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties

Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii

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

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