PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy

Autores
Gaurón, María Celeste; Newton, Alexandra C.; Colombo, Maria Isabel
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hijacking the autophagic machinery is a key mechanism through which invasive pathogens such as Staphylococcus aureus replicate in their host cells. We have previously demonstrated that the bacteria replicate in phagosomes labeled with the autophagic protein LC3, before escaping to the cytoplasm. Here, we show that the Ca2+-dependent PKCα binds to S. aureus-containing phagosomes and that α-hemolysin, secreted by S. aureus, promotes this recruitment of PKCα to phagosomal membranes. Interestingly, the presence of PKCα prevents the association of the autophagic protein LC3. Live cell imaging experiments using the PKC activity reporter CKAR reveal that treatment of cells with S. aureus culture supernatants containing staphylococcal secreted factors transiently activates PKC. Functional studies reveal that overexpression of PKCα causes a marked inhibition of bacterial replication. Taken together, our data identify enhancing PKCα activity as a potential approach to inhibit S. aureus replication in mammalian cells.
Fil: Gaurón, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University of California at San Diego; Estados Unidos
Fil: Newton, Alexandra C.. University of California at San Diego; Estados Unidos
Fil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Materia
AUTOPHAGY
LC3
PROTEIN KINASE C
STAPHYLOCOCCUS AUREUS
XENOPHAGY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174636
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagyGaurón, María CelesteNewton, Alexandra C.Colombo, Maria IsabelAUTOPHAGYLC3PROTEIN KINASE CSTAPHYLOCOCCUS AUREUSXENOPHAGYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Hijacking the autophagic machinery is a key mechanism through which invasive pathogens such as Staphylococcus aureus replicate in their host cells. We have previously demonstrated that the bacteria replicate in phagosomes labeled with the autophagic protein LC3, before escaping to the cytoplasm. Here, we show that the Ca2+-dependent PKCα binds to S. aureus-containing phagosomes and that α-hemolysin, secreted by S. aureus, promotes this recruitment of PKCα to phagosomal membranes. Interestingly, the presence of PKCα prevents the association of the autophagic protein LC3. Live cell imaging experiments using the PKC activity reporter CKAR reveal that treatment of cells with S. aureus culture supernatants containing staphylococcal secreted factors transiently activates PKC. Functional studies reveal that overexpression of PKCα causes a marked inhibition of bacterial replication. Taken together, our data identify enhancing PKCα activity as a potential approach to inhibit S. aureus replication in mammalian cells.Fil: Gaurón, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University of California at San Diego; Estados UnidosFil: Newton, Alexandra C.. University of California at San Diego; Estados UnidosFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFrontiers Media2021-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174636Gaurón, María Celeste; Newton, Alexandra C.; Colombo, Maria Isabel; PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy; Frontiers Media; Frontiers in Immunology; 12; 3-2021; 1-131664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2021.662987/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.662987info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:16:43Zoai:ri.conicet.gov.ar:11336/174636instacron: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:34982025-10-22 12:16:43.441CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
title PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
spellingShingle PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
Gaurón, María Celeste
AUTOPHAGY
LC3
PROTEIN KINASE C
STAPHYLOCOCCUS AUREUS
XENOPHAGY
title_short PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
title_full PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
title_fullStr PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
title_full_unstemmed PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
title_sort PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy
dc.creator.none.fl_str_mv Gaurón, María Celeste
Newton, Alexandra C.
Colombo, Maria Isabel
author Gaurón, María Celeste
author_facet Gaurón, María Celeste
Newton, Alexandra C.
Colombo, Maria Isabel
author_role author
author2 Newton, Alexandra C.
Colombo, Maria Isabel
author2_role author
author
dc.subject.none.fl_str_mv AUTOPHAGY
LC3
PROTEIN KINASE C
STAPHYLOCOCCUS AUREUS
XENOPHAGY
topic AUTOPHAGY
LC3
PROTEIN KINASE C
STAPHYLOCOCCUS AUREUS
XENOPHAGY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Hijacking the autophagic machinery is a key mechanism through which invasive pathogens such as Staphylococcus aureus replicate in their host cells. We have previously demonstrated that the bacteria replicate in phagosomes labeled with the autophagic protein LC3, before escaping to the cytoplasm. Here, we show that the Ca2+-dependent PKCα binds to S. aureus-containing phagosomes and that α-hemolysin, secreted by S. aureus, promotes this recruitment of PKCα to phagosomal membranes. Interestingly, the presence of PKCα prevents the association of the autophagic protein LC3. Live cell imaging experiments using the PKC activity reporter CKAR reveal that treatment of cells with S. aureus culture supernatants containing staphylococcal secreted factors transiently activates PKC. Functional studies reveal that overexpression of PKCα causes a marked inhibition of bacterial replication. Taken together, our data identify enhancing PKCα activity as a potential approach to inhibit S. aureus replication in mammalian cells.
Fil: Gaurón, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University of California at San Diego; Estados Unidos
Fil: Newton, Alexandra C.. University of California at San Diego; Estados Unidos
Fil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
description Hijacking the autophagic machinery is a key mechanism through which invasive pathogens such as Staphylococcus aureus replicate in their host cells. We have previously demonstrated that the bacteria replicate in phagosomes labeled with the autophagic protein LC3, before escaping to the cytoplasm. Here, we show that the Ca2+-dependent PKCα binds to S. aureus-containing phagosomes and that α-hemolysin, secreted by S. aureus, promotes this recruitment of PKCα to phagosomal membranes. Interestingly, the presence of PKCα prevents the association of the autophagic protein LC3. Live cell imaging experiments using the PKC activity reporter CKAR reveal that treatment of cells with S. aureus culture supernatants containing staphylococcal secreted factors transiently activates PKC. Functional studies reveal that overexpression of PKCα causes a marked inhibition of bacterial replication. Taken together, our data identify enhancing PKCα activity as a potential approach to inhibit S. aureus replication in mammalian cells.
publishDate 2021
dc.date.none.fl_str_mv 2021-03
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/11336/174636
Gaurón, María Celeste; Newton, Alexandra C.; Colombo, Maria Isabel; PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy; Frontiers Media; Frontiers in Immunology; 12; 3-2021; 1-13
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174636
identifier_str_mv Gaurón, María Celeste; Newton, Alexandra C.; Colombo, Maria Isabel; PKCα is recruited to staphylococcus aureus-containing phagosomes and impairs bacterial replication by inhibition of autophagy; Frontiers Media; Frontiers in Immunology; 12; 3-2021; 1-13
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2021.662987/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2021.662987
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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
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score 12.982451

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