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

Date

2017-05

Authors

Kao, Wei-Chien Andrew
Pětrošová, Helena
Ebady, Rhodaba
Lithgow, Karen V.
Rojas, Pablo
Zhang, Yang
Kim, Yae-Eun
Kim, Yae-Ram
Odisho, Tanya
Gupta, Nupur

Journal Title

Journal ISSN

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Publisher

Scientific Reports

Abstract

Treponema 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.

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Citation

Kao, 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. https://doi.org/10.1038/s41598-017-01589-4