Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete
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 s...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/24434a553c8f4861988c1a974bab078c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:24434a553c8f4861988c1a974bab078c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:24434a553c8f4861988c1a974bab078c2021-12-02T12:30:35ZIdentification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete10.1038/s41598-017-01589-42045-2322https://doaj.org/article/24434a553c8f4861988c1a974bab078c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01589-4https://doaj.org/toc/2045-2322Abstract 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.Wei-Chien Andrew KaoHelena PětrošováRhodaba EbadyKaren V. LithgowPablo RojasYang ZhangYae-Eun KimYae-Ram KimTanya OdishoNupur GuptaAnnette MoterCaroline E. CameronTara J. MoriartyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Wei-Chien Andrew Kao Helena Pětrošová Rhodaba Ebady Karen V. Lithgow Pablo Rojas Yang Zhang Yae-Eun Kim Yae-Ram Kim Tanya Odisho Nupur Gupta Annette Moter Caroline E. Cameron Tara J. Moriarty Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| description |
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. |
| format |
article |
| author |
Wei-Chien Andrew Kao Helena Pětrošová Rhodaba Ebady Karen V. Lithgow Pablo Rojas Yang Zhang Yae-Eun Kim Yae-Ram Kim Tanya Odisho Nupur Gupta Annette Moter Caroline E. Cameron Tara J. Moriarty |
| author_facet |
Wei-Chien Andrew Kao Helena Pětrošová Rhodaba Ebady Karen V. Lithgow Pablo Rojas Yang Zhang Yae-Eun Kim Yae-Ram Kim Tanya Odisho Nupur Gupta Annette Moter Caroline E. Cameron Tara J. Moriarty |
| author_sort |
Wei-Chien Andrew Kao |
| title |
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| title_short |
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| title_full |
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| title_fullStr |
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| title_full_unstemmed |
Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme disease Spirochete |
| title_sort |
identification of tp0751 (pallilysin) as a treponema pallidum vascular adhesin by heterologous expression in the lyme disease spirochete |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/24434a553c8f4861988c1a974bab078c |
| work_keys_str_mv |
AT weichienandrewkao identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT helenapetrosova identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT rhodabaebady identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT karenvlithgow identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT pablorojas identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT yangzhang identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT yaeeunkim identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT yaeramkim identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT tanyaodisho identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT nupurgupta identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT annettemoter identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT carolineecameron identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete AT tarajmoriarty identificationoftp0751pallilysinasatreponemapallidumvascularadhesinbyheterologousexpressioninthelymediseasespirochete |
| _version_ |
1718394322092556288 |