A Novel Laminin-Binding Protein Mediates Microbial-Endothelial Cell Interactions and Facilitates Dissemination of Lyme Disease Pathogens

Bista, Sandhya; Singh, Preeti; Bernard, Quentin; Yang, Xiuli; Hart, Thomas; Lin, Yi‐Pin; Kitsou, Chrysoula; Rana, Vipin Singh; Zhang, Fuming; Linhardt, Robert J.; Zhnag, Kai; Akins, Darrin R.; Hritzo, Lucy; Kim, Yuri; Grab, Dennis J.; Dumler, J. Stephen; Pal, Utpal

doi:10.1093/infdis/jiz626

Cited by 8 publications

(12 citation statements)

References 38 publications

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“…In response to changing environmental conditions, B. burgdorferi replicates rapidly in the midgut during and following tick feeding, with the number of Borrelia increasing from <500 prior to feeding to about 1.7 x 10 5 per tick after 72 hours of feeding, a >300-fold increase (De Silva and Fikrig, 1995) (Ristow et al, 2015). BB0406, which like P66 potentially may serve as a porin and an adhesin, facilitates B. burgdorferi infection (Shrestha et al, 2017;Bista et al, 2020). Several nutrient salvage proteins required for survival in mammalian tissue have been identified (Table 1).…”

Section: Genes and Proteins Involved In Infection And Pathogenesismentioning

confidence: 99%

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Lyme Disease Pathogenesis

Coburn¹,

Garcia²,

Hu³

et al. 2022

Current Issues in Molecular Biology

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Lyme disease Borrelia are obligately parasitic, ticktransmitted, invasive, persistent bacterial pathogens that cause disease in humans and non-reservoir vertebrates primarily through the induction of inflammation. During transmission from the infected tick, the bacteria undergo significant changes in gene expression, resulting in adaptation to the mammalian environment. The organisms multiply and spread locally and induce inflammatory responses that, in humans, result in clinical signs and symptoms. Borrelia virulence involves a multiplicity of mechanisms for dissemination and colonization of multiple tissues and evasion of host immune responses. Most of the tissue damage, which is seen in non-reservoir hosts, appears to result from host inflammatory reactions, despite the low numbers of bacteria in affected sites. This host response to the Lyme disease Borrelia can cause neurologic, cardiovascular, arthritic, and dermatologic manifestations during the disseminated and persistent stages of infection. The mechanisms by which a paucity of organisms (in comparison to many other infectious diseases) can cause varied and in some cases profound inflammation and symptoms remains mysterious but are the subjects of diverse ongoing investigations. In this review, we provide an overview of virulence mechanisms and determinants for which roles have been demonstrated in vivo, primarily in mouse models of infection.Prokaryotes evolved approximately 3.5 billion years ago (Schopf, 2000) and, by definition, were initially free-living. The evolution of microbial communities and symbiotic relationships about 1 billion years ago eventually resulted in the development of multicellular eukaryotic organisms, creating new ecologic niches. Bacteria colonized these caister.com/cimb 473 Curr.

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Section: Genes and Proteins Involved In Infection And Pathogenesismentioning

confidence: 99%

“…BB0406 is a recent addition to the group of lamininbinding adhesins as well as a putative porin (Shrestha et al, 2017;Bista et al, 2020). Mutants in bb0406 are infectious but attenuated in mice and show reduced bacterial burdens in tissues compared to the parental strain.…”

Section: Adhesins That Bind To Extracellular Matrix Componentsmentioning

confidence: 99%

Lyme Disease Pathogenesis

Coburn¹,

Garcia²,

Hu³

et al. 2022

Current Issues in Molecular Biology

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“…2, 3B ). Candidate joint mediators identified previously by intravenous phage display, intravital microscopy and infectivity studies include Lmp1, BB0406, BB0347, OspC and VlsE, as well as P66, an integral membrane protein that mediates joint vascular transmigration but not EC surface interactions 3,16,25,41,42,44,45 . These candidates bind a wide range of host molecules that could potentially be involved in joint vascular interactions and dissemination, including glycosaminoglycans, laminin, fibronectin, plasminogen and integrins.…”

Section: Main Textmentioning

confidence: 99%

“…Although B. garinii DbpA/B has been found to support HUVEC interactions in flow chambers, B. burgdorferi N40 DbpA/B does not 46 , and the potential contributions of the B. burgdorferi B31 DbpA/B strain variant used in our studies to EC interactions and intravenous dissemination to skin have not been examined. Other candidates identified in intravenous infectivity studies are BB0406, P66 and the fibronectin-binding adhesin RevA 16,44 .…”

Section: Main Textmentioning

confidence: 99%

Vascular tropism models of blood-borne microbial dissemination

Ebady

et al. 2021

Preprint

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SUMMARYSimilar to circulating tumour and immune cells, many blood-borne microbes preferentially “home” to specific vascular sites and tissues during hematogenous dissemination 1–5. For many pathogens, the “postal codes” and mechanisms responsible for tissue-specific vascular tropism are unknown and have been challenging to unravel. Members of the Lyme disease Borreliella burgdorferi species complex infect a broad range of mammalian tissues and exhibit complex strain-, species- and host-specific tissue tropism patterns. Intravenous perfusion experiments and intravital microscopy studies suggest that heterogeneous tissue tropism properties may depend on tissue-specific differences in host and microbial molecules supporting vascular interaction and extravasation. However, interpreting these studies can be complicated because of the immune-protective moonlighting (multitasking) properties of many B. burgdorferi adhesins. Here, we investigated whether B. burgdorferi vascular interaction properties measured by live cell imaging and particle tracking in aorta, bladder, brain, joint and skin microvascular flow chamber models predict strain- and tissue-specific dissemination patterns in vivo These studies identified strain- and endothelial cell type-specific interaction properties that accurately predicted in vivo dissemination of B. burgdorferi to bladder, brain, joint and skin but not aorta, and indicated that dissemination mechanisms in all of these tissues are distinct. Thus, the ability to interact with vascular surfaces under physiological shear stress is a key determinant of tissue-specific tropism for Lyme disease bacteria. The methods and model systems reported here will be invaluable for identifying and characterizing the diverse, largely undefined molecules and mechanisms supporting dissemination of Lyme disease bacteria. These methods and models may be useful for studying tissue tropism and vascular dissemination mechanisms of other blood-borne microbes.

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“…Once Lyme borreliae make the initial adherence contact with the endothelium they are able to transmigrate across the endothelium and reach the distant tissues (Moriarty et al., 2008; Norman et al., 2008). There are a few studies where it has been shown that Lyme borreliae are also able to transmigrate across the endothelial barrier of the brain microvasculature (Bista et al., 2020; Grab et al., 2005, 2009; Nyarko et al., 2006; Pulzova et al., 2011), while no studies have been published on the initial adhesion of Lyme borreliae to human brain microvascular endothelial cells (HBMECs).…”

Section: Introductionmentioning

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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A Novel Laminin-Binding Protein Mediates Microbial-Endothelial Cell Interactions and Facilitates Dissemination of Lyme Disease Pathogens

Cited by 8 publications

References 38 publications

Lyme Disease Pathogenesis

Lyme Disease Pathogenesis

Vascular tropism models of blood-borne microbial dissemination

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

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