ArticlePLoS pathogens2016
Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 124 citations in OpenAlex.
- Many hosts, many solutions: How reservoirs shape Borrelia protein diversity.PLoS pathogens · 2026Article
- Complement inhibition by a unique cluster of immunomodulatory outer surface proteins of Borrelia recurrentis.Nature communications · 2026Article
- Modulator-induced conformational changes in complement C5, implications for function and drug design.Frontiers in immunology · 2026Article
- Borrelia surface proteins: new horizons in Lyme disease diagnosis.Applied microbiology and biotechnology · 2025Review
- Advantages of using complement components in preventive and therapeutic vaccine strategies for infectious and non-infectious diseases.Journal of the Royal Society, Interface · 2025Review
- Heterologous Surface Display Reveals Conserved Complement Inhibition and Functional Diversification of Borrelia burgdorferi Elp Proteins.Molecular microbiology · 2025Article
- BBK32 attenuates antibody-dependent complement-mediated killing of infectious Borreliella burgdorferi isolates.PLoS pathogens · 2025Article
- Navigating infection by pathogenic spirochetes: The host-bacteria interface at the atomic level.Protein science : a publication of the Protein Society · 2025Review
- Borrelia burgdorferi serine protease HtrA is a pleiotropic regulator of stress response, motility, flagellar hemostasis, and infectivity.Communications biology · 2025Article
- RecombinantPathogens (Basel, Switzerland) · 2024Article
- Unprecedented genetic variability of PFam54 paralogs among Eurasian Lyme borreliosis-causing spirochetes.Ecology and evolution · 2024Article
- Suppression of host humoral immunity byInfection and immunity · 2024Article
- Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- A tick saliva serpin, IxsS17 inhibits host innate immune system proteases and enhances host colonization by Lyme disease agent.PLoS pathogens · 2024Article
- Multifunctional interaction of CihC/FbpC orthologs of relapsing fever spirochetes with host-derived proteins involved in adhesion, fibrinolysis, and complement evasion.Frontiers in immunology · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- A chemosensory-like histidine kinase is dispensable for chemotaxis in vitro but regulates the virulence of Borrelia burgdorferi through modulating the stability of RpoS.PLoS pathogens · 2023Article
- Antibody Cross-Reactivity in Serodiagnosis of Lyme Disease.Antibodies (Basel, Switzerland) · 2023Review
- Functional and structural analyses reveal that a dual domain sialidase protects bacteria from complement killing through desialylation of complement factors.PLoS pathogens · 2023Article
- Structural evolution of an immune evasion determinant shapes pathogen host tropism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pathogens that traffic in blood, lymphatics, or interstitial fluids must adopt strategies to evade innate immune defenses, notably the complement system. Through recruitment of host regulators of complement to their surface, many pathogens are able to escape complement-mediated attack. The Lyme disease spirochete, Borrelia burgdorferi, produces a number of surface proteins that bind to factor H related molecules, which function as the dominant negative regulator of the alternative pathway of complement. Relatively less is known about how B. burgdorferi evades the classical pathway of complement despite the observation that some sensu lato strains are sensitive to classical pathway activation. Here we report that the borrelial lipoprotein BBK32 potently and specifically inhibits the classical pathway by binding with high affinity to the initiating C1 complex of complement. In addition, B. burgdorferi cells that produce BBK32 on their surface bind to both C1 and C1r and a serum sensitive derivative of B. burgdorferi is protected from killing via the classical pathway in a BBK32-dependent manner. Subsequent biochemical and biophysical approaches localized the anti-complement activity of BBK32 to its globular C-terminal domain. Mechanistic studies reveal that BBK32 acts by entrapping C1 in its zymogen form by binding and inhibiting the C1 subcomponent, C1r, which serves as the initiating serine protease of the classical pathway. To our knowledge this is the first report of a spirochetal protein acting as a direct inhibitor of the classical pathway and is the only example of a biomolecule capable of specifically and noncovalently inhibiting C1/C1r. By identifying a unique mode of complement evasion this study greatly enhances our understanding of how pathogens subvert and potentially manipulate host innate immune systems.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.