Interaction between Borrelia burgdorferi and endothelium in vitro.

Szczepanski, Andrew; Furie, Martha B.; Benach, Jorge L.; Lane, Bernard; Fleit, Howard B.

doi:10.1172/jci114615

Cited by 175 publications

(155 citation statements)

References 40 publications

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“…Motility has long been believed to be essential for dissemination of B. burgdorferi from the site of inoculation and subsequent invasion of mammalian host tissues (61,62). The linkage between motility and infectivity for mammals recently was strengthened by intravital imaging of blood-borne spirochetes in mice; following attachment to the vascular endothelium, B. burgdorferi move toward and then rapidly penetrate endothelial cell junctions (63,64).…”

Section: Discussionmentioning

confidence: 99%

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

et al. 2009

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Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven.

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Section: Discussionmentioning

confidence: 99%

Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks

et al. 2009

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“…Consistent with the ability of B. burgdorferi to cause multisystemic infection, the spirochete can attach to a variety of cell types (8)(9)(10)(11)(12)(13). Proteoglycans, a class of ubiquitously expressed host cell molecules, are among the mammalian cell components that are recognized by this pathogen (14)(15)(16).…”

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confidence: 95%

Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi , the Lyme disease spirochete

Fischer

Parveen

Magoun

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

108

148

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Host cell binding is an essential step in colonization by many bacterial pathogens, and the Lyme disease agent, Borrelia burgdorferi, which colonizes multiple tissues, is capable of attachment to diverse cell types. Glycosaminoglycans (GAGs) are ubiquitously expressed on mammalian cells and are recognized by multiple B. burgdorferi surface proteins. We previously showed that B. burgdorferi strains differ in the particular spectrum of GAGs that they recognize, leading to differences in the cultured mammalian cell types that they efficiently bind. The molecular basis of these binding specificities remains undefined, due to the difficulty of analyzing multiple, potentially redundant cell attachment pathways and to the paucity of genetic tools for this pathogen. In the current study, we show that the expression of decorin-binding protein (

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“…In vitro, B. burgdorferi attach to a variety of endothelial and epithelial cells (7)(8)(9)(10)(11) and to the subendothelial cell matrix (7), but the nature of the ligand(s) or the receptor(s) is not clearly established ( 12). These observations combined with the multiple organ system involvement seen in clinical infection (4) suggest that at least one mode ofB.…”

Section: Introductionmentioning

confidence: 99%