Cargando…
The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carr...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036719/ https://www.ncbi.nlm.nih.gov/pubmed/21347378 http://dx.doi.org/10.1371/journal.pone.0016879 |
_version_ | 1782197891353280512 |
---|---|
author | Choy, Henry A. Kelley, Melissa M. Croda, Julio Matsunaga, James Babbitt, Jane T. Ko, Albert I. Picardeau, Mathieu Haake, David A. |
author_facet | Choy, Henry A. Kelley, Melissa M. Croda, Julio Matsunaga, James Babbitt, Jane T. Ko, Albert I. Picardeau, Mathieu Haake, David A. |
author_sort | Choy, Henry A. |
collection | PubMed |
description | Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats. |
format | Text |
id | pubmed-3036719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30367192011-02-23 The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans Choy, Henry A. Kelley, Melissa M. Croda, Julio Matsunaga, James Babbitt, Jane T. Ko, Albert I. Picardeau, Mathieu Haake, David A. PLoS One Research Article Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats. Public Library of Science 2011-02-09 /pmc/articles/PMC3036719/ /pubmed/21347378 http://dx.doi.org/10.1371/journal.pone.0016879 Text en 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. 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 Choy, Henry A. Kelley, Melissa M. Croda, Julio Matsunaga, James Babbitt, Jane T. Ko, Albert I. Picardeau, Mathieu Haake, David A. The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans |
title | The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
|
title_full | The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
|
title_fullStr | The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
|
title_full_unstemmed | The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
|
title_short | The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
|
title_sort | multifunctional ligb adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic leptospira interrogans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036719/ https://www.ncbi.nlm.nih.gov/pubmed/21347378 http://dx.doi.org/10.1371/journal.pone.0016879 |
work_keys_str_mv | AT choyhenrya themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT kelleymelissam themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT crodajulio themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT matsunagajames themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT babbittjanet themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT koalberti themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT picardeaumathieu themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT haakedavida themultifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT choyhenrya multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT kelleymelissam multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT crodajulio multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT matsunagajames multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT babbittjanet multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT koalberti multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT picardeaumathieu multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans AT haakedavida multifunctionalligbadhesinbindshomeostaticproteinswithpotentialrolesincutaneousinfectionbypathogenicleptospirainterrogans |