Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules

Autores
Boudreau, Marc A.; Fishovitz, Jennifer; Llarrull, Leticia Irene; Xiao, Qiaobin; Mobashery, Shahriar
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β- lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibioticresistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria.
Fil: Boudreau, Marc A.. University Of Notre Dame-Indiana; Estados Unidos
Fil: Fishovitz, Jennifer. University Of Notre Dame-Indiana; Estados Unidos
Fil: Llarrull, Leticia Irene. University Of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Xiao, Qiaobin. University Of Notre Dame-Indiana; Estados Unidos
Fil: Mobashery, Shahriar. University Of Notre Dame-Indiana; Estados Unidos
Materia
Blar1
Phosphorylation
Mrsa
Kinase Inhibitor
Stk1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/21386
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/21386
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small MoleculesBoudreau, Marc A.Fishovitz, JenniferLlarrull, Leticia IreneXiao, QiaobinMobashery, ShahriarBlar1PhosphorylationMrsaKinase InhibitorStk1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β- lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibioticresistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria.Fil: Boudreau, Marc A.. University Of Notre Dame-Indiana; Estados UnidosFil: Fishovitz, Jennifer. University Of Notre Dame-Indiana; Estados UnidosFil: Llarrull, Leticia Irene. University Of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Xiao, Qiaobin. University Of Notre Dame-Indiana; Estados UnidosFil: Mobashery, Shahriar. University Of Notre Dame-Indiana; Estados UnidosAmerican Chemical Society2015-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21386Boudreau, Marc A.; Fishovitz, Jennifer; Llarrull, Leticia Irene; Xiao, Qiaobin; Mobashery, Shahriar; Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules; American Chemical Society; ACS Infectious Diseases; 1; 10; 8-2015; 454-4592373-8227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acsinfecdis.5b00086info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsinfecdis.5b00086info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:42:13Zoai:ri.conicet.gov.ar:11336/21386instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:42:13.331CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
title Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
spellingShingle Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
Boudreau, Marc A.
Blar1
Phosphorylation
Mrsa
Kinase Inhibitor
Stk1
title_short Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
title_full Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
title_fullStr Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
title_full_unstemmed Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
title_sort Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules
dc.creator.none.fl_str_mv Boudreau, Marc A.
Fishovitz, Jennifer
Llarrull, Leticia Irene
Xiao, Qiaobin
Mobashery, Shahriar
author Boudreau, Marc A.
author_facet Boudreau, Marc A.
Fishovitz, Jennifer
Llarrull, Leticia Irene
Xiao, Qiaobin
Mobashery, Shahriar
author_role author
author2 Fishovitz, Jennifer
Llarrull, Leticia Irene
Xiao, Qiaobin
Mobashery, Shahriar
author2_role author
author
author
author
dc.subject.none.fl_str_mv Blar1
Phosphorylation
Mrsa
Kinase Inhibitor
Stk1
topic Blar1
Phosphorylation
Mrsa
Kinase Inhibitor
Stk1
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β- lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibioticresistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria.
Fil: Boudreau, Marc A.. University Of Notre Dame-Indiana; Estados Unidos
Fil: Fishovitz, Jennifer. University Of Notre Dame-Indiana; Estados Unidos
Fil: Llarrull, Leticia Irene. University Of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Xiao, Qiaobin. University Of Notre Dame-Indiana; Estados Unidos
Fil: Mobashery, Shahriar. University Of Notre Dame-Indiana; Estados Unidos
description Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β- lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibioticresistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21386
Boudreau, Marc A.; Fishovitz, Jennifer; Llarrull, Leticia Irene; Xiao, Qiaobin; Mobashery, Shahriar; Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules; American Chemical Society; ACS Infectious Diseases; 1; 10; 8-2015; 454-459
2373-8227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21386
identifier_str_mv Boudreau, Marc A.; Fishovitz, Jennifer; Llarrull, Leticia Irene; Xiao, Qiaobin; Mobashery, Shahriar; Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules; American Chemical Society; ACS Infectious Diseases; 1; 10; 8-2015; 454-459
2373-8227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acsinfecdis.5b00086
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsinfecdis.5b00086
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613330288771072
score 13.070432

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