Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete

dc.contributor.authorKao, Wei-Chien Andrew
dc.contributor.authorPětrošová, Helena
dc.contributor.authorEbady, Rhodaba
dc.contributor.authorLithgow, Karen V.
dc.contributor.authorRojas, Pablo
dc.contributor.authorZhang, Yang
dc.contributor.authorKim, Yae-Eun
dc.contributor.authorKim, Yae-Ram
dc.contributor.authorOdisho, Tanya
dc.contributor.authorGupta, Nupur
dc.contributor.authorMoter, Annette
dc.contributor.authorCameron, Caroline E.
dc.contributor.authorMoriarty, Tara J.
dc.description.abstractTreponema pallidum subsp. pallidum, the causative agent of syphilis, is a highly invasive spirochete pathogen that uses the vasculature to disseminate throughout the body. Identification of bacterial factors promoting dissemination is crucial for syphilis vaccine development. An important step in dissemination is bacterial adhesion to blood vessel surfaces, a process mediated by bacterial proteins that can withstand forces imposed on adhesive bonds by blood flow (vascular adhesins). The study of T. pallidum vascular adhesins is hindered by the uncultivable nature of this pathogen. We overcame these limitations by expressing T. pallidum adhesin Tp0751 (pallilysin) in an adhesion-attenuated strain of the cultivable spirochete Borrelia burgdorferi. Under fluid shear stress representative of conditions in postcapillary venules, Tp0751 restored bacterial-vascular interactions to levels similar to those observed for infectious B. burgdorferi and a gain-of-function strain expressing B. burgdorferi vascular adhesin BBK32. The strength and stability of Tp0751-and BBK32-dependent endothelial interactions under physiological shear stress were similar, although the mechanisms stabilizing these interactions were distinct. Tp0751 expression also permitted bacteria to interact with postcapillary venules in live mice as effectively as BBK32-expressing strains. These results demonstrate that Tp0751 can function as a vascular adhesin.en_US
dc.description.sponsorshipWe thank N Zlotnikov for assistance with figure preparation and S Houston for critical manuscript review, A Bansal, A Javid and C Lo for technical assistance, and G Chaconas for bacterial strains. We are also grateful for expert assistance from staff and use of facilities at the Sick Kids Imaging Facility, and University of Toronto Faculty of Medicine Department of Comparative Medicine. This project was supported by the following operating and infrastructure funding: Canadian Institutes of Health Research (CIHR) (MOP-11959 and ICS-12398), Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN 401), Banting Research Foundation, University of Toronto, Faculty of Dentistry Enrichment Fund and Bertha Rosenstadt Endowment Fund and Canada Foundation for Innovation/Ontario Research Fund (CFI/ORF) (27881) to T.J.M.; National Institutes of Health (NIH) (AI-015334, NSERC (327186) and CIHR Canada Research Chairs (CRC) Program to C.E.C.; Heart & Stroke Richard Lewar Centre for Excellence (HSRLCE) in Cardiovascular Research postdoctoral fellowship to H.P.; Harron Fellowship and University of Toronto Graduate Fellowship to R.E.; University of Toronto Graduate Fellowship to W.C.K.; NSERC CGS-D graduate scholarship to K.L.V.; German DAAD exchange scholarship to P.R.; CIHR IMHA undergraduate summer studentship award to Y.Z.en_US
dc.identifier.citationKao, W.A.; Pětrošová, H.; Ebady, R.; Lithgow, K.V.; Rojas, P.; Zhang, Y.; … & Moriarty, T. (2017). Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete. Scientific Reports, 7, article 1538.
dc.publisherScientific Reportsen_US
dc.titleIdentification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirocheteen_US


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