Faculty Collaboration Database

VlsE, the nexus for antigenic variation of the Lyme disease spirochete, also mediates early bacterial attachment to the host microvasculature under shear force. PLoS Pathog 2022 May;18(5):e1010511

Date

05/24/2022

Pubmed ID

35605029

Pubmed Central ID

PMC9166660

DOI

10.1371/journal.ppat.1010511

Scopus ID

2-s2.0-85131457166 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Hematogenous dissemination is a critical step in the evolution of local infection to systemic disease. The Lyme disease (LD) spirochete, which efficiently disseminates to multiple tissues, has provided a model for this process, in particular for the key early event of pathogen adhesion to the host vasculature. This occurs under shear force mediated by interactions between bacterial adhesins and mammalian cell-surface proteins or extracellular matrix (ECM). Using real-time intravital imaging of the Lyme spirochete in living mice, we previously identified BBK32 as the first LD spirochetal adhesin demonstrated to mediate early vascular adhesion in a living mouse; however, deletion of bbk32 resulted in loss of only about half of the early interactions, suggesting the existence of at least one other adhesin (adhesin-X) that promotes early vascular interactions. VlsE, a surface lipoprotein, was identified long ago by its capacity to undergo rapid antigenic variation, is upregulated in the mammalian host and required for persistent infection in immunocompetent mice. In immunodeficient mice, VlsE shares functional overlap with OspC, a multi-functional protein that displays dermatan sulfate-binding activity and is required for joint invasion and colonization. In this research, using biochemical and genetic approaches as well as intravital imaging, we have identified VlsE as adhesin-X; it is a dermatan sulfate (DS) adhesin that efficiently promotes transient adhesion to the microvasculature under shear force via its DS binding pocket. Intravenous inoculation of mice with a low-passage infectious B. burgdorferi strain lacking both bbk32 and vlsE almost completely eliminated transient microvascular interactions. Comparative analysis of binding parameters of VlsE, BBK32 and OspC provides a possible explanation why these three DS adhesins display different functionality in terms of their ability to promote early microvascular interactions.

Author List

Tan X, Lin YP, Pereira MJ, Castellanos M, Hahn BL, Anderson P, Coburn J, Leong JM, Chaconas G

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adhesins, Bacterial
Animals
Antigenic Variation
Antigens, Bacterial
Bacterial Adhesion
Bacterial Outer Membrane Proteins
Bacterial Proteins
Borrelia burgdorferi
Dermatan Sulfate
Lipoproteins
Lyme Disease
Mammals
Mice
Microvessels
Shear Strength