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Dissemination is a critical stage of disease progression by the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yme spirochaete, <jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>orrelia burgdorferi<\/jats:italic>. However, many mechanistic features of the process are not yet understood. A key step is adhesion of circulating microbes to vascular surfaces in the face of the shear forces present in flowing blood. Using real\u2010time microscopic imaging of the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yme spirochaete in living mice we previously identified the first bacterial protein (<jats:italic><jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>.\u2009burgdorferi<\/jats:italic> <jats:styled-content style=\"fixed-case\">BBK<\/jats:styled-content>32) shown to mediate vascular adhesion <jats:italic>in vivo.<\/jats:italic> Vascular adhesion is also dependent on host fibronectin (<jats:styled-content style=\"fixed-case\">Fn<\/jats:styled-content>) and glycosaminoglycans (<jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content>s). In the present study, we investigated the mechanisms of <jats:styled-content style=\"fixed-case\">BBK<\/jats:styled-content>32\u2010dependent vascular adhesion <jats:italic>in vivo<\/jats:italic>. We determined that <jats:styled-content style=\"fixed-case\">BBK<\/jats:styled-content>32\u2013<jats:styled-content style=\"fixed-case\">Fn<\/jats:styled-content> interactions (tethering) function as a molecular braking mechanism that permits the formation of more stable <jats:styled-content style=\"fixed-case\">BBK<\/jats:styled-content>32\u2013<jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content> interactions (dragging) between circulating bacteria and vascular surfaces. Since <jats:styled-content style=\"fixed-case\">BBK<\/jats:styled-content>32\u2010like proteins are expressed in a variety of pathogens we believe that the vascular adhesion mechanisms we have deciphered here may be critical for understanding the dissemination mechanisms of other bacterial pathogens.<\/jats:p>","DOI":"10.1111\/mmi.12045","type":"journal-article","created":{"date-parts":[[2012,10,24]],"date-time":"2012-10-24T10:16:19Z","timestamp":1351073779000},"page":"1116-1131","source":"Crossref","is-referenced-by-count":87,"title":["Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules"],"prefix":"10.1111","volume":"86","author":[{"given":"Tara J.","family":"Moriarty","sequence":"first","affiliation":[{"name":"Matrix Dynamics Group, Faculty of Dentistry, and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine University of Toronto  ON M5S\u20093E2 Canada"},{"name":"Snyder Institute for Chronic Diseases, Departments of Biochemistry &amp; 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