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Plasma fibronectin stabilizes Borrelia burgdorferi-endothelial interactions under vascular shear stress by a catch-bond mechanism

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Abstract

Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined. Fibronectin (Fn), a ubiquitous host molecule targeted by many pathogens, promotes vascular interactions of the Lyme disease spirochete Borrelia burgdorferi. Here, we investigated how B. burgdorferi exploits Fn to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial-endothelial interaction biomechanics. We found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn (pFn), an abundant protein in blood plasma that is normally soluble and nonadhesive. Under physiological shear stress, caps of polymerized pFn at bacterial poles formed part of mechanically loaded adhesion complexes, and pFn strengthened and stabilized interactions by a catch-bond mechanism. These results show that B. burgdorferi can transform a ubiquitous but normally nonadhesive blood constituent to increase the efficiency, strength, and stability of bacterial interactions with vascular surfaces. Similar mechanisms may promote dissemination of other Fn-binding pathogens.

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Niddam, A. F., Ebady, R., Bansal, A., Koehler, A., Hinz, B., & Moriarty, T. J. (2017). Plasma fibronectin stabilizes Borrelia burgdorferi-endothelial interactions under vascular shear stress by a catch-bond mechanism. Proceedings of the National Academy of Sciences of the United States of America, 114(17), E3490–E3498. https://doi.org/10.1073/pnas.1615007114

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