Borrelia burgdorferi Infection in Biglycan Knockout Mice

Cuellar, Julia; Pietikäinen, Annukka; Glader, Otto; Liljenbäck, Heidi; Söderström, Mirva; Hurme, Saija; Salo, Jemiina; Hytönen, Jukka

doi:10.1093/infdis/jiz050

Cited by 8 publications

(8 citation statements)

References 33 publications

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“…Lyme borreliae bind to GAGs and proteoglycans, − and such binding activity facilitates spirochete attachment to mammalian cells/tissues under static ,− or shear stressed conditions. − ,− Among those ligands, decorin, biglycan, and dermatan sulfate were reported to bind to spirochetes, promoting tissue colonization of spirochetes and Lyme disease-associated manifestations. ,,− We found that Lyme borreliae species and strains display a universal capability of binding to NACH, an analog of GAGs. We also demonstrated that NACH-treated spirochetes display reduced binding ability to different purified GAGs and proteoglycans, compared to untreated bacteria.…”

Section: Discussionmentioning

confidence: 94%

“…Vertebrate hosts generate multiple receptors on the cell surface that are exploited by microbes including Lyme borreliae to facilitate its tissue colonization. , One such receptor type is a proteoglycan (e.g., decorin and biglycan), which is composed of a core protein and covalently linked glycan chains, as known as glycosaminoglycans (GAGs). − Lyme borreliae less efficiently colonize the tissues of mice defective in producing decorin or biglycan. , These spirochetes were also documented to bind to these proteoglycans and several GAGs, including heparan sulfate and dermatan sulfate, − and the incubation of these molecules with Lyme borreliae inhibits spirochete attachment to the cells. , These results suggest that a spirochete’s ability to bind to a proteoglycan or GAG mediates its attachment to host cells and tissues. Furthermore, intravenous inoculation of B. burgdorferi in conjunction with heparin, a GAG analog, reduces the vascular interaction of spirochetes. , This result supports the use of heparin to prevent hematogenous dissemination of Lyme borreliae.…”

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confidence: 99%

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Non-anticoagulant Heparin as a Pre-exposure Prophylaxis Prevents Lyme Disease Infection

Lin

Marcinkiewicz

et al. 2020

ACS Infect. Dis.

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Experimental timeline of NACH inoculation and tick infection in mice (Figure S1); replete ticks acquiring blood from NACH-or PBStreated mice displaying similar weight and spirochete burdens (Figure S2); spirochetes being undetectable at 56 days post-tick feeding of NACH-treated mice (Figure S3); strains used in this study (Table S1); the generation time of PBS-and NACH-treated B. burgdorferi strains used in this study (Table S2); primers used in this study (Table S3) (PDF)

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Non-anticoagulant Heparin as a Pre-exposure Prophylaxis Prevents Lyme Disease Infection

Lin

Marcinkiewicz

et al. 2020

ACS Infect. Dis.

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“…Escherichia coli strain M15 (Qiagen, Hilden, Germany) was used for cloning and expression of Dbps (Heikkilä et al., 2002a, 2002b). E. coli DH5α was used to purify pME22 plasmid containing the dbpBA operon of B. garinii SBK40 (infectious strain both in mice and men (Cuellar et al., 2019; Heikkilä et al., 2002b)). E. coli XL10‐Gold (Agilent, Santa Clara, CA) was used in cloning of site‐directed mutants.…”

Section: Methodsmentioning

confidence: 99%

Conserved lysine residues in decorin binding proteins ofBorrelia gariniiare critical in adhesion to human brain microvascular endothelial cells

Pietikäinen

Åstrand

Cuellar

et al. 2021

Molecular Microbiology

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Lyme borreliosis is a tick‐borne disease caused by Borrelia burgdorferi sensu lato spirochetes (Lyme borreliae). When the disease affects the central nervous system, it is referred to as neuroborreliosis. In Europe, neuroborreliosis is most often caused by Borrelia garinii. Although it is known that in the host Lyme borreliae spread from the tick bite site to distant tissues via the blood vasculature, the adherence of Lyme borreliae to human brain microvascular endothelial cells has not been studied before. Decorin binding proteins are adhesins expressed on Lyme borreliae. They mediate the adhesion of Lyme borreliae to decorin and biglycan, and the lysine residues located in the binding site of decorin binding proteins are important to the binding activity. In this study, we show that lysine residues located in the canonical binding site can also be found in decorin binding proteins of Borrelia garinii, and that these lysines contribute to biglycan and decorin binding. Most importantly, we show that the lysine residues are crucial for the binding of Lyme borreliae to decorin and biglycan expressing human brain microvascular endothelial cells, which in turn suggests that they are involved in the pathogenesis of neuroborreliosis.

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“…The course of infection was followed by collecting ear biopsy samples at days 7, 11, 14, and 21 postinfection and measuring the lateral diameter of the hind joints, in a blinded manner, once a week. After 28 days postinfection, ear, bladder, heart, and joint samples were collected for Borrelia culture and qPCR analyses, as described earlier (45,46), as well as serum for serological analyses.…”

Section: Methodsmentioning

confidence: 99%

Structural and Biomolecular Analyses of Borrelia burgdorferi BmpD Reveal a Substrate-Binding Protein of an ABC-Type Nucleoside Transporter Family

et al. 2020

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Borrelia burgdorferi sensu lato, the causative agent of tick-borne Lyme borreliosis (LB), has a limited metabolic capacity and needs to acquire nutrients, such as amino acids, fatty acids, and nucleic acids, from the host environment. Using X-ray crystallography, liquid chromatography-mass spectrometry, microscale thermophoresis, and cellular localization studies, we show that basic membrane protein D (BmpD) is a periplasmic substrate-binding protein of an ABC transporter system binding to purine nucleosides. Nucleosides are essential for bacterial survival in the host organism, and these studies suggest a key role for BmpD in the purine salvage pathway of B. burgdorferi sensu lato. Because B. burgdorferi sensu lato lacks the enzymes required for de novo purine synthesis, BmpD may play a vital role in ensuring access to the purines needed to sustain an infection in the host. Furthermore, we show that, although human LB patients develop anti-BmpD antibodies, immunization of mice with BmpD does not confer protection against B. burgdorferi sensu lato infection.

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Borrelia burgdorferi Infection in Biglycan Knockout Mice

Cited by 8 publications

References 33 publications

Non-anticoagulant Heparin as a Pre-exposure Prophylaxis Prevents Lyme Disease Infection

Non-anticoagulant Heparin as a Pre-exposure Prophylaxis Prevents Lyme Disease Infection

Conserved lysine residues in decorin binding proteins ofBorrelia gariniiare critical in adhesion to human brain microvascular endothelial cells

Structural and Biomolecular Analyses of Borrelia burgdorferi BmpD Reveal a Substrate-Binding Protein of an ABC-Type Nucleoside Transporter Family

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