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The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis

Staphylococcus aureus is a prominent bacterial pathogen that is known to agglutinate in the presence of human plasma to form stable clumps. There is increasing evidence that agglutination aids S. aureus pathogenesis, but the mechanisms of this process remain to be fully elucidated. To better define...

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Autores principales: Walker, Jennifer N., Crosby, Heidi A., Spaulding, Adam R., Salgado-Pabón, Wilmara, Malone, Cheryl L., Rosenthal, Carolyn B., Schlievert, Patrick M., Boyd, Jeffrey M., Horswill, Alexander R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868527/
https://www.ncbi.nlm.nih.gov/pubmed/24367264
http://dx.doi.org/10.1371/journal.ppat.1003819
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author Walker, Jennifer N.
Crosby, Heidi A.
Spaulding, Adam R.
Salgado-Pabón, Wilmara
Malone, Cheryl L.
Rosenthal, Carolyn B.
Schlievert, Patrick M.
Boyd, Jeffrey M.
Horswill, Alexander R.
author_facet Walker, Jennifer N.
Crosby, Heidi A.
Spaulding, Adam R.
Salgado-Pabón, Wilmara
Malone, Cheryl L.
Rosenthal, Carolyn B.
Schlievert, Patrick M.
Boyd, Jeffrey M.
Horswill, Alexander R.
author_sort Walker, Jennifer N.
collection PubMed
description Staphylococcus aureus is a prominent bacterial pathogen that is known to agglutinate in the presence of human plasma to form stable clumps. There is increasing evidence that agglutination aids S. aureus pathogenesis, but the mechanisms of this process remain to be fully elucidated. To better define this process, we developed both tube based and flow cytometry methods to monitor clumping in the presence of extracellular matrix proteins. We discovered that the ArlRS two-component system regulates the agglutination mechanism during exposure to human plasma or fibrinogen. Using divergent S. aureus strains, we demonstrated that arlRS mutants are unable to agglutinate, and this phenotype can be complemented. We found that the ebh gene, encoding the Giant Staphylococcal Surface Protein (GSSP), was up-regulated in an arlRS mutant. By introducing an ebh complete deletion into an arlRS mutant, agglutination was restored. To assess whether GSSP is the primary effector, a constitutive promoter was inserted upstream of the ebh gene on the chromosome in a wildtype strain, which prevented clump formation and demonstrated that GSSP has a negative impact on the agglutination mechanism. Due to the parallels of agglutination with infective endocarditis development, we assessed the phenotype of an arlRS mutant in a rabbit combined model of sepsis and endocarditis. In this model the arlRS mutant displayed a large defect in vegetation formation and pathogenesis, and this phenotype was partially restored by removing GSSP. Altogether, we have discovered that the ArlRS system controls a novel mechanism through which S. aureus regulates agglutination and pathogenesis.
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spelling pubmed-38685272013-12-23 The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis Walker, Jennifer N. Crosby, Heidi A. Spaulding, Adam R. Salgado-Pabón, Wilmara Malone, Cheryl L. Rosenthal, Carolyn B. Schlievert, Patrick M. Boyd, Jeffrey M. Horswill, Alexander R. PLoS Pathog Research Article Staphylococcus aureus is a prominent bacterial pathogen that is known to agglutinate in the presence of human plasma to form stable clumps. There is increasing evidence that agglutination aids S. aureus pathogenesis, but the mechanisms of this process remain to be fully elucidated. To better define this process, we developed both tube based and flow cytometry methods to monitor clumping in the presence of extracellular matrix proteins. We discovered that the ArlRS two-component system regulates the agglutination mechanism during exposure to human plasma or fibrinogen. Using divergent S. aureus strains, we demonstrated that arlRS mutants are unable to agglutinate, and this phenotype can be complemented. We found that the ebh gene, encoding the Giant Staphylococcal Surface Protein (GSSP), was up-regulated in an arlRS mutant. By introducing an ebh complete deletion into an arlRS mutant, agglutination was restored. To assess whether GSSP is the primary effector, a constitutive promoter was inserted upstream of the ebh gene on the chromosome in a wildtype strain, which prevented clump formation and demonstrated that GSSP has a negative impact on the agglutination mechanism. Due to the parallels of agglutination with infective endocarditis development, we assessed the phenotype of an arlRS mutant in a rabbit combined model of sepsis and endocarditis. In this model the arlRS mutant displayed a large defect in vegetation formation and pathogenesis, and this phenotype was partially restored by removing GSSP. Altogether, we have discovered that the ArlRS system controls a novel mechanism through which S. aureus regulates agglutination and pathogenesis. Public Library of Science 2013-12-19 /pmc/articles/PMC3868527/ /pubmed/24367264 http://dx.doi.org/10.1371/journal.ppat.1003819 Text en © 2013 Walker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Walker, Jennifer N.
Crosby, Heidi A.
Spaulding, Adam R.
Salgado-Pabón, Wilmara
Malone, Cheryl L.
Rosenthal, Carolyn B.
Schlievert, Patrick M.
Boyd, Jeffrey M.
Horswill, Alexander R.
The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title_full The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title_fullStr The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title_full_unstemmed The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title_short The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis
title_sort staphylococcus aureus arlrs two-component system is a novel regulator of agglutination and pathogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868527/
https://www.ncbi.nlm.nih.gov/pubmed/24367264
http://dx.doi.org/10.1371/journal.ppat.1003819
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