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Identification of Cell-Binding Adhesins of Leptospira interrogans

Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of patho...

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Autores principales: Evangelista, Karen V., Hahn, Beth, Wunder, Elsio A., Ko, Albert I., Haake, David A., Coburn, Jenifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183468/
https://www.ncbi.nlm.nih.gov/pubmed/25275630
http://dx.doi.org/10.1371/journal.pntd.0003215
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author Evangelista, Karen V.
Hahn, Beth
Wunder, Elsio A.
Ko, Albert I.
Haake, David A.
Coburn, Jenifer
author_facet Evangelista, Karen V.
Hahn, Beth
Wunder, Elsio A.
Ko, Albert I.
Haake, David A.
Coburn, Jenifer
author_sort Evangelista, Karen V.
collection PubMed
description Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA.hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1–130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines.
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spelling pubmed-41834682014-10-07 Identification of Cell-Binding Adhesins of Leptospira interrogans Evangelista, Karen V. Hahn, Beth Wunder, Elsio A. Ko, Albert I. Haake, David A. Coburn, Jenifer PLoS Negl Trop Dis Research Article Leptospirosis is a globally distributed bacterial infectious disease caused by pathogenic members of the genus Leptospira. Infection can lead to illness ranging from mild and non-specific to severe, with jaundice, kidney and liver dysfunction, and widespread endothelial damage. The adhesion of pathogenic Leptospira species (spp.), the causative agent of leptospirosis, to host tissue components is necessary for infection and pathogenesis. While it is well-established that extracellular matrix (ECM) components play a role in the interaction of the pathogen with host molecules, we have shown that pathogenic Leptospira interrogans binds to host cells more efficiently than to ECM components. Using in vitro phage display to select for phage clones that bind to EA.hy926 endothelial cells, we identified the putative lipoproteins LIC10508 and LIC13411, and the conserved hypothetical proteins LIC12341 and LIC11574, as candidate L. interrogans sv. Copenhageni st. Fiocruz L1–130 adhesins. Recombinant LIC11574, but not its L. biflexa homologue LBF1629, exhibited dose-dependent binding to both endothelial and epithelial cells. In addition, LIC11574 and LIC13411 bind to VE-cadherin, an endothelial cell receptor for L. interrogans. Extraction of bacteria with the non-ionic detergent Triton X-114 resulted in partitioning of the candidate adhesins to the detergent fraction, a likely indication that these proteins are outer membrane localized. All candidate adhesins were recognized by sera obtained from leptospirosis patients but not by sera from healthy individuals as assessed by western blot. This work has identified bacterial adhesins that are potentially involved in L. interrogans infection of the mammalian host, and through cadherin binding, may contribute to dissemination and vascular damage. Our findings may be of value in leptospirosis control and prevention, with the bacterial adhesins potentially serving as targets for development of diagnostics, therapeutics, and vaccines. Public Library of Science 2014-10-02 /pmc/articles/PMC4183468/ /pubmed/25275630 http://dx.doi.org/10.1371/journal.pntd.0003215 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Evangelista, Karen V.
Hahn, Beth
Wunder, Elsio A.
Ko, Albert I.
Haake, David A.
Coburn, Jenifer
Identification of Cell-Binding Adhesins of Leptospira interrogans
title Identification of Cell-Binding Adhesins of Leptospira interrogans
title_full Identification of Cell-Binding Adhesins of Leptospira interrogans
title_fullStr Identification of Cell-Binding Adhesins of Leptospira interrogans
title_full_unstemmed Identification of Cell-Binding Adhesins of Leptospira interrogans
title_short Identification of Cell-Binding Adhesins of Leptospira interrogans
title_sort identification of cell-binding adhesins of leptospira interrogans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183468/
https://www.ncbi.nlm.nih.gov/pubmed/25275630
http://dx.doi.org/10.1371/journal.pntd.0003215
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