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:	Jennifer N Walker, Heidi A Crosby, Adam R Spaulding, Wilmara Salgado-Pabón, Cheryl L Malone, Carolyn B Rosenthal, Patrick M Schlievert, Jeffrey M Boyd, Alexander R Horswill
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b43cf5c3e76c432eaa1f4d0f87311ac3
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spelling	oai:doaj.org-article:b43cf5c3e76c432eaa1f4d0f87311ac32021-11-18T06:07:13ZThe Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis.1553-73661553-737410.1371/journal.ppat.1003819https://doaj.org/article/b43cf5c3e76c432eaa1f4d0f87311ac32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24367264/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Staphylococcus 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.Jennifer N WalkerHeidi A CrosbyAdam R SpauldingWilmara Salgado-PabónCheryl L MaloneCarolyn B RosenthalPatrick M SchlievertJeffrey M BoydAlexander R HorswillPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 12, p e1003819 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jennifer N Walker Heidi A Crosby Adam R Spaulding Wilmara Salgado-Pabón Cheryl L Malone Carolyn B Rosenthal Patrick M Schlievert Jeffrey M Boyd Alexander R Horswill The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis.
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.
format	article
author	Jennifer N Walker Heidi A Crosby Adam R Spaulding Wilmara Salgado-Pabón Cheryl L Malone Carolyn B Rosenthal Patrick M Schlievert Jeffrey M Boyd Alexander R Horswill
author_facet	Jennifer N Walker Heidi A Crosby Adam R Spaulding Wilmara Salgado-Pabón Cheryl L Malone Carolyn B Rosenthal Patrick M Schlievert Jeffrey M Boyd Alexander R Horswill
author_sort	Jennifer N Walker
title	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_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_sort	staphylococcus aureus arlrs two-component system is a novel regulator of agglutination and pathogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b43cf5c3e76c432eaa1f4d0f87311ac3
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The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis.

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