Complement evasion strategies of <i>Borrelia burgdorferi</i> sensu lato

Dulipati, Vinaya; Meri, Seppo; Panelius, Jaana

doi:10.1002/1873-3468.13894

Cited by 39 publications

(41 citation statements)

References 90 publications

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“…All three pathways result in the formation of enzymatic complexes that trigger the release of proinflammatory peptides, the opsonization of the microbe, and the formation of a membrane attack complex (MAC) that lyses the pathogen. To promote survival during tick feeding and/or spread within the vertebrate host, B. burgdorferi encodes surface lipoproteins that inhibit key steps of complement activation (9,10,71). B. burgdorferi OspC (Outer surface protein C), a lipoprotein essential to the spirochete life cycle, binds to C4b to inhibit B. burgdorferi bloodstream clearance (15).…”

Section: Introductionmentioning

confidence: 99%

Lipoproteome screening of the Lyme disease agent identifies novel inhibitors of antibody-mediated complement killing

Pereira

Wager

Garrigues

et al. 2021

Preprint

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Spirochetal pathogens such as the causative agent of Lyme disease, Borrelia burgdorferi sensu lato, encode an abundance of lipoproteins; however, due in part to their evolutionary distance from more well-studied bacteria such as Proteobacteria and Firmicutes, very few spirochetal lipoproteins have assigned functions. Indeed, B. burgdorferi devotes almost 8% of its genome to lipoprotein genes and interacts with its environment primarily through the production of at least eighty surface-exposed lipoproteins throughout its tick vector-vertebrate host lifecycle (57). Several B. burgdorferi lipoproteins have been shown to serve diverse roles, such as cellular adherence or immune evasion, but the functions for most B. burgdorferi surface lipoproteins remain unknown. In this study, we developed a B. burgdorferi lipoproteome screening platform utilizing intact spirochetes that enables the identification of previously unrecognized host interactions. As spirochetal survival in the bloodstream is essential for dissemination, we targeted our screen to C1, the first component of the classical (antibody-mediated) complement pathway. We identified two high-affinity C1 interactions by the paralogous lipoproteins, ErpB and ErpQ. Using biochemical, microbiological, and biophysical approaches, we demonstrated that ErpB and ErpQ inhibit the activated forms of the C1 proteases, C1r and C1s, and represent a new mechanistic class of C1 inhibitors that protect the spirochete from antibody-mediated complement killing by allosteric regulation. In addition to identifying a novel mode of complement inhibition, our study establishes a lipoproteome screening methodology as a discovery platform for identifying direct host-pathogen interactions that are central to the pathogenesis of spirochetes, such as the Lyme disease agent.

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Section: Introductionmentioning

confidence: 99%

Lipoproteome screening of the Lyme disease agent identifies novel inhibitors of antibody-mediated complement killing

Pereira

Wager

Garrigues

et al. 2021

Preprint

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“…Simultaneous to the disappearance of OspA, the spirochaetes population in the gut of the tick begin to express OspC. Osp A, Osp B and Osp D are overexpressed in Borrelia burgdorferi during ticks' colonization while Osp C, Osp E [173] and Osp F are overexpressed when Borrelia burgdorferi is in the mammalian host [174,175]. Osp A and Osp B are lipoproteins of the outer membrane of B. burgdorferi, of which the apparent molecular weight among the different species of B. burgdorferi sensu lato is 30-33 kDa for OspA and 34 kDa for Osp B [176].…”

Section: Outer Surface Protein (Osp)mentioning

confidence: 99%

Borreliae Part 1: Borrelia Lyme Group and Echidna-Reptile Group

Trevisan

Cinco

Trevisini

et al. 2021

Biology

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Borreliae are divided into three groups, namely the Lyme group (LG), the Echidna-Reptile group (REPG) and the Relapsing Fever group (RFG). Currently, only Borrelia of the Lyme and RF groups (not all) cause infection in humans. Borreliae of the Echidna-Reptile group represent a new monophyletic group of spirochaetes, which infect amphibians and reptiles. In addition to a general description of the phylum Spirochaetales, including a brief historical digression on spirochaetosis, in the present review Borreliae of Lyme and Echidna-Reptile groups are described, discussing the ecology with vectors and hosts as well as microbiological features and molecular characterization. Furthermore, differences between LG and RFG are discussed with respect to the clinical manifestations. In humans, LG Borreliae are organotropic and cause erythema migrans in the early phase of the disease, while RFG Borreliae give high spirochaetemia with fever, without the development of erythema migrans. With respect of LG Borreliae, recently Borrelia mayonii, with intermediate characteristics between LG and RFG, has been identified. As part of the LG, it gives erythema migrans but also high spirochaetemia with fever. Hard ticks are vectors for both LG and REPG groups, but in LG they are mostly Ixodes sp. ticks, while in REPG vectors do not belong to that genus.

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“…Borrelia spp. pathogens activate all complement pathways, even in the absence of Borrelia specific antibodies [110]. Therefore, they have acquired several mechanisms by which they can escape complement killing, including the exploitation of tick salivary components.…”

Section: Complementmentioning

confidence: 99%

Changing the Recipe: Pathogen Directed Changes in Tick Saliva Components

Pham

Underwood

Chávez

2021

IJERPH

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Ticks are obligate hematophagous parasites and are important vectors of a wide variety of pathogens. These pathogens include spirochetes in the genus Borrelia that cause Lyme disease, rickettsial pathogens, and tick-borne encephalitis virus, among others. Due to their prolonged feeding period of up to two weeks, hard ticks must counteract vertebrate host defense reactions in order to survive and reproduce. To overcome host defense mechanisms, ticks have evolved a large number of pharmacologically active molecules that are secreted in their saliva, which inhibits or modulates host immune defenses and wound healing responses upon injection into the bite site. These bioactive molecules in tick saliva can create a privileged environment in the host’s skin that tick-borne pathogens take advantage of. In fact, evidence is accumulating that tick-transmitted pathogens manipulate tick saliva composition to enhance their own survival, transmission, and evasion of host defenses. We review what is known about specific and functionally characterized tick saliva molecules in the context of tick infection with the genus Borrelia, the intracellular pathogen Anaplasma phagocytophilum, and tick-borne encephalitis virus. Additionally, we review studies analyzing sialome-level responses to pathogen challenge.

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Complement evasion strategies of Borrelia burgdorferi sensu lato

Cited by 39 publications

References 90 publications

Lipoproteome screening of the Lyme disease agent identifies novel inhibitors of antibody-mediated complement killing

Lipoproteome screening of the Lyme disease agent identifies novel inhibitors of antibody-mediated complement killing

Borreliae Part 1: Borrelia Lyme Group and Echidna-Reptile Group

Changing the Recipe: Pathogen Directed Changes in Tick Saliva Components

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