Flow-Tolerant Adhesion of a Bacterial Pathogen to Human Endothelial Cells Through Interaction With Biglycan

Salo, Jemiina; Pietikäinen, Annukka; Söderström, Mirva; Auvinen, Kaisa; Salmi, Marko; Ebady, Rhodaba; Moriarty, Tara J.; Viljanen, Matti K.; Hytönen, Jukka

doi:10.1093/infdis/jiw003

Cited by 16 publications

(30 citation statements)

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“…In addition to BBK32, a number of other vascular adhesins have recently been identified in B . burgdorferi (BB0347, and decorin-binding proteins DbpA and DbpB) 31–33 and in Staphylococcus aureus (von Willebrand factor-binding protein, vWbp, and fibronectin-binding protein A, FnBPA) 34, 35 . All of these adhesins, including BBK32, share the property of binding to glycosylated structures and/or extracellular matrix components of blood and endothelial cells, including von Willebrand factor and fibronectin (Fn) 33, 36–39 .…”

Section: Introductionmentioning

confidence: 99%

Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete

Kao

Pětrošová

Ebady

et al. 2017

Sci Rep

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Treponema pallidum subsp. pallidum, the causative agent of syphilis, is a highly invasive spirochete pathogen that uses the vasculature to disseminate throughout the body. Identification of bacterial factors promoting dissemination is crucial for syphilis vaccine development. An important step in dissemination is bacterial adhesion to blood vessel surfaces, a process mediated by bacterial proteins that can withstand forces imposed on adhesive bonds by blood flow (vascular adhesins). The study of T. pallidum vascular adhesins is hindered by the uncultivable nature of this pathogen. We overcame these limitations by expressing T. pallidum adhesin Tp0751 (pallilysin) in an adhesion-attenuated strain of the cultivable spirochete Borrelia burgdorferi. Under fluid shear stress representative of conditions in postcapillary venules, Tp0751 restored bacterial-vascular interactions to levels similar to those observed for infectious B. burgdorferi and a gain-of-function strain expressing B. burgdorferi vascular adhesin BBK32. The strength and stability of Tp0751-and BBK32-dependent endothelial interactions under physiological shear stress were similar, although the mechanisms stabilizing these interactions were distinct. Tp0751 expression also permitted bacteria to interact with postcapillary venules in live mice as effectively as BBK32-expressing strains. These results demonstrate that Tp0751 can function as a vascular adhesin.Treponema pallidum subsp. pallidum is a bacterium from the spirochete family and the causative agent of syphilis. Syphilis is a sexually transmitted disease, which is often considered a disease of the past. However, it still represents a global health problem with 36 million cases and 11 million new infections annually 1 . Moreover, syphilis incidence has increased dramatically over the past two decades in Canada 2 , the United States 3 , China 4 , and in a number of European countries [5][6][7] . Given its high prevalence, syphilis has a substantial impact on global health. Syphilis infection in pregnancy has up to 80% morbidity and can result in stillbirth, neonatal death, and complications associated with congenital syphilis in newborns 8 . Active syphilis infection also significantly increases infectivity of HIV-positive patients and risk of HIV acquisition 9 , and modeling studies suggest that controlling syphilis will contribute to HIV prevention 10 . Since elimination of syphilis has not been achieved by antibiotic treatment, novel preventative approaches are needed to fight this disease.To date, the molecular mechanisms of T. pallidum pathogenesis are still poorly understood. This is mainly because the organism is an obligate human pathogen that cannot be cultured continuously in vitro 11 . The inability to culture T. pallidum has limited the use of many experimental approaches, including genetic manipulation to

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Section: Introductionmentioning

confidence: 99%

Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete

Kao

Pětrošová

Ebady

et al. 2017

Sci Rep

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“…It is possible that B burgdorferi may evade serologic detection by residing in immune‐privileged sites such as the eye and central nervous system. It has been shown in the literature that Borrelia has the ability to adhere to the vascular endothelium via decorin‐binding proteins and resist the force of blood flow 32,33 . This may help Borrelia to colonize specific organs.…”

Section: Discussionmentioning

confidence: 99%

Ocular disease in horses with confirmed ocular or central nervous system Borrelia infection: Case series and review of literature

Scherrer

Knickelbein

Engiles

et al. 2020

Veterinary Ophthalmology

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Objective To describe the clinical presentation, treatment, and clinical outcome of horses with ocular disease and evidence of systemic or ocular Lyme disease. Animals Studied Five horses met the inclusion criteria of ocular disease with evidence of B burgdorferi present in ocular or CNS tissues. Procedure The goal of this study was to describe the clinical presentation and progression of ocular disease when associated with ocular or CNS B burgdorferi infection in horses. A retrospective review of medical records was performed on horses admitted for ocular disease with evidence of B burgdorferi infection between 1998 and 2015. The diagnosis of B burgdorferi‐associated uveitis was based on histopathologic lesions of lymphohistiocytic and suppurative uveitis/endophthalmitis and intralesional argyrophilic spirochetes in either ocular or CNS tissue consistent with Borrelia. Leptospiral uveitis was ruled out by PCR. Results All five horses in the current study had intraocular inflammation at the time of presentation. Medical management with anti‐inflammatories was successful in controlling uveitis in the two horses in which treatment of uveitis was attempted. Systemic treatment with oral tetracyclines was unsuccessful in a single case in which treatment of Borrelia was attempted. Four horses were euthanized due to progression of neurologic disease. The surviving horse had an enucleation performed and did not show systemic signs. Conclusions Infection with Borrelia burgdorferi should be considered in endemic areas as a differential for horses with ocular disease, in particular, uveitis. The prognosis for uveitis and neurologic disease associated with Lyme disease was poor in the current study.

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“…However, a small number of studies have attempted to compare the functional roles of some infection-associated proteins present in European Borrelia species. A popular strategy is to use a non-infectious, easily transformable, isogenic strain, such as B. burgdorferi B313 or B314, and insert allelic variants of virulence genes from different borrelial strains [75][76][77]. An alternative method is to use deletion mutants of the highly transformable infectious strain B. burgdorferi ss.…”

Section: Delineation Of the Protein Function In European Borrelia Spementioning

confidence: 99%

The need to unravel the twisted nature of the Borrelia burgdorferi sensu lato complex across Europe

Strnad

Rego

2020

Microbiology

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Lyme borreliosis is a vector-borne infection caused by bacteria under the Borrelia burgdorferi sensu lato complex, both in Europe and North America. Differential gene expression at different times throughout its infectious cycle allows the spirochete to survive very diverse environments within different mammalian hosts as well as the tick vector. To date, the vast majority of data about spirochetal proteins and their functions are from genetic studies carried out on North American strains of a single species, i.e. B. burgdorferi sensu stricto. The whole-genome sequences recently obtained for several European species/strains make it feasible to adapt and use genetic techniques to study inherent differences between them. This review highlights the crucial need to undertake independent studies of genospecies within Europe, given their varying genetic content and pathogenic potential, and differences in clinical manifestation.

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Flow-Tolerant Adhesion of a Bacterial Pathogen to Human Endothelial Cells Through Interaction With Biglycan

Abstract: The proteoglycan biglycan is a receptor molecule for flow-resistant adhesion of the bacterial pathogen B. garinii on human endothelial cells.

Cited by 16 publications

References 45 publications

Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete

Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete

Ocular disease in horses with confirmed ocular or central nervous system Borrelia infection: Case series and review of literature

The need to unravel the twisted nature of the Borrelia burgdorferi sensu lato complex across Europe

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