The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines

11 pag, 6 figs. Coordinates for the model of SrrB DHp-CA region solved by X-ray crystallography have been deposited in the Protein Data Bank, https://www.rcsb.org/ (ID code 6PAJ). This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1921307117/-/D...

Descripción completa

Detalles Bibliográficos
Autores: Tiwari, Nitija, López-Redondo, Marisa, Miguel-Romero, Laura, Kulhankova, Katarina, Cahill, Michael P., Tran, Phuong M., Kinney, Kyle J., Kilgore, Samuel H., Al-Tameemi, Hassan, Herfst, Christine A., Tuffs, Stephen W., Kirby, John R., Boyd, Jeffery M., McCormick, John K., Salgado-Pabón, Wilmara, Marina, Alberto, Schlievert, Patrick M., Fuentes, Ernesto J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/214702
Acceso en línea:http://hdl.handle.net/10261/214702
Access Level:acceso abierto
Palabra clave:SrrAB two-component system
Staphylococcus aureus
Cysteine disulfide bond
Sensor histidine kinase
id ES_37b32f3eae5ea42491c1d35de5f2a2ee
oai_identifier_str oai:digital.csic.es:10261/214702
network_acronym_str ES
network_name_str España
repository_id_str
spelling The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteinesTiwari, NitijaLópez-Redondo, MarisaMiguel-Romero, LauraKulhankova, KatarinaCahill, Michael P.Tran, Phuong M.Kinney, Kyle J.Kilgore, Samuel H.Al-Tameemi, HassanHerfst, Christine A.Tuffs, Stephen W.Kirby, John R.Boyd, Jeffery M.McCormick, John K.Salgado-Pabón, WilmaraMarina, AlbertoSchlievert, Patrick M.Fuentes, Ernesto J.SrrAB two-component systemStaphylococcus aureusCysteine disulfide bondSensor histidine kinase11 pag, 6 figs. Coordinates for the model of SrrB DHp-CA region solved by X-ray crystallography have been deposited in the Protein Data Bank, https://www.rcsb.org/ (ID code 6PAJ). This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1921307117/-/DCSupplemental.Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.This work was supported by funding from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) to E.J.F. and P.M.S. (NIAID Grant AI135305). J.M.B. was funded by the NIH (NIAID Grant AI139100-01) and US Department of Agriculture Multistate Reseach Fund (Project NE−1028). W.S.-P. was supported by NIH (NIAID Grant AI134692-03). The J.K.M. lab was supported by the Canadian Institutes of Health Research (Grant PJT-166050). A.M. was supported by grant BIO2016-78571-P from the Ministerio de Economia y Competitividad (Spain).Peer reviewedNational Academy of Sciences (U.S.)National Institutes of Health (US)National Institute of Allergy and Infectious Diseases (US)Department of Agriculture (US)Canadian Institutes of Health ResearchMinisterio de Economía y Competitividad (España)Marina, Alberto [0000-0002-1334-5273]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/214702reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-78571-Phttp://dx.doi.org/10.1073/pnas.1921307117Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2147022026-05-22T06:33:51Z
dc.title.none.fl_str_mv The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
title The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
spellingShingle The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
Tiwari, Nitija
SrrAB two-component system
Staphylococcus aureus
Cysteine disulfide bond
Sensor histidine kinase
title_short The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
title_full The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
title_fullStr The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
title_full_unstemmed The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
title_sort The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines
dc.creator.none.fl_str_mv Tiwari, Nitija
López-Redondo, Marisa
Miguel-Romero, Laura
Kulhankova, Katarina
Cahill, Michael P.
Tran, Phuong M.
Kinney, Kyle J.
Kilgore, Samuel H.
Al-Tameemi, Hassan
Herfst, Christine A.
Tuffs, Stephen W.
Kirby, John R.
Boyd, Jeffery M.
McCormick, John K.
Salgado-Pabón, Wilmara
Marina, Alberto
Schlievert, Patrick M.
Fuentes, Ernesto J.
author Tiwari, Nitija
author_facet Tiwari, Nitija
López-Redondo, Marisa
Miguel-Romero, Laura
Kulhankova, Katarina
Cahill, Michael P.
Tran, Phuong M.
Kinney, Kyle J.
Kilgore, Samuel H.
Al-Tameemi, Hassan
Herfst, Christine A.
Tuffs, Stephen W.
Kirby, John R.
Boyd, Jeffery M.
McCormick, John K.
Salgado-Pabón, Wilmara
Marina, Alberto
Schlievert, Patrick M.
Fuentes, Ernesto J.
author_role author
author2 López-Redondo, Marisa
Miguel-Romero, Laura
Kulhankova, Katarina
Cahill, Michael P.
Tran, Phuong M.
Kinney, Kyle J.
Kilgore, Samuel H.
Al-Tameemi, Hassan
Herfst, Christine A.
Tuffs, Stephen W.
Kirby, John R.
Boyd, Jeffery M.
McCormick, John K.
Salgado-Pabón, Wilmara
Marina, Alberto
Schlievert, Patrick M.
Fuentes, Ernesto J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Institutes of Health (US)
National Institute of Allergy and Infectious Diseases (US)
Department of Agriculture (US)
Canadian Institutes of Health Research
Ministerio de Economía y Competitividad (España)
Marina, Alberto [0000-0002-1334-5273]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv SrrAB two-component system
Staphylococcus aureus
Cysteine disulfide bond
Sensor histidine kinase
topic SrrAB two-component system
Staphylococcus aureus
Cysteine disulfide bond
Sensor histidine kinase
description 11 pag, 6 figs. Coordinates for the model of SrrB DHp-CA region solved by X-ray crystallography have been deposited in the Protein Data Bank, https://www.rcsb.org/ (ID code 6PAJ). This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1921307117/-/DCSupplemental.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/214702
url http://hdl.handle.net/10261/214702
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-78571-P
http://dx.doi.org/10.1073/pnas.1921307117
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406054048071680
score 15,81155

Similares en LA Referencia