α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells

Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly leading to staphylococ...

Full description

Bibliographic Details
Authors: Mestre, María Belén, Fader Kaiser, Claudio Marcelo, Sola, Claudia del Valle, Colombo, María Isabel
Format: article
Status:Published version
Publication Date:2010
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/189126
Online Access:http://hdl.handle.net/11336/189126
Access Level:Open access
Keyword:AUTOPHAGY
LC3
STAPHYLOCOCCUS AUREUS
TOXIN
Α-HEMOLYSIN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
id AR_4e078fd4deed6e81b7eb18121eece5f0
oai_identifier_str oai:ri.conicet.gov.ar:11336/189126
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
title α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
spellingShingle α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
Mestre, María Belén
AUTOPHAGY
LC3
STAPHYLOCOCCUS AUREUS
TOXIN
Α-HEMOLYSIN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
title_full α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
title_fullStr α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
title_full_unstemmed α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
title_sort α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells
dc.creator.none.fl_str_mv Mestre, María Belén
Fader Kaiser, Claudio Marcelo
Sola, Claudia del Valle
Colombo, María Isabel
author Mestre, María Belén
author_facet Mestre, María Belén
Fader Kaiser, Claudio Marcelo
Sola, Claudia del Valle
Colombo, María Isabel
author_role author
author2 Fader Kaiser, Claudio Marcelo
Sola, Claudia del Valle
Colombo, María Isabel
author2_role author
author
author
dc.subject.none.fl_str_mv AUTOPHAGY
LC3
STAPHYLOCOCCUS AUREUS
TOXIN
Α-HEMOLYSIN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic AUTOPHAGY
LC3
STAPHYLOCOCCUS AUREUS
TOXIN
Α-HEMOLYSIN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly leading to staphylococcal persistence and chronic disease. It has been previously shown that this pathogen localizes to LC3-labeled compartments and subverts the autophagy pathway. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. In the present report we present evidence that the pore-forming toxin α-hemolysin (hla) is a S. aureus secreted factor which participates in the activation of the autophagic pathway. In addition, our results indicate that although the toxin elicits an autophagic response this pathway is dysfunctional as indicated by the accumulation of the LC3-II form in cell lysates obtained from intoxicated cells. In addition, not only the purified hla toxin but also the toxin-secreting pathogen prevented the maturation of autophagosomes. Interestingly, in cells infected with the wild-type strain of S. aureus the bacteria-containing compartments which recruited LC3 onto the limiting membrane did not accumulate the acidotropic probe LysoTracker. In contrast, those phagosomes containing the hla(-) mutant (unable to produce the toxin) localized in an acidic compartment unlabeled by LC3. These results suggest that the LC3 protein is recruited only to those damaged vacuoles (i.e., perforated by the toxin), perhaps as an attempt to protect the cells. Furthermore, we have demonstrated that the toxin-dependent activation of autophagy (although it is regulated by calcium and requires Atg5) is independent of both PI3Kinase activity and Beclin 1 suggesting the involvement of a non-canonical autophagy pathway. © 2010 Landes Bioscience.
publishDate 2010
dc.date.none.fl_str_mv 2010-01
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/11336/189126
Mestre, María Belén; Fader Kaiser, Claudio Marcelo; Sola, Claudia del Valle; Colombo, María Isabel; α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells; Landes Bioscience; Autophagy; 6; 1; 1-2010; 110-125
1554-8627
1554-8635
CONICET Digital
CONICET
url http://hdl.handle.net/11336/189126
identifier_str_mv Mestre, María Belén; Fader Kaiser, Claudio Marcelo; Sola, Claudia del Valle; Colombo, María Isabel; α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells; Landes Bioscience; Autophagy; 6; 1; 1-2010; 110-125
1554-8627
1554-8635
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://pubmed.ncbi.nlm.nih.gov/20110774/
info:eu-repo/semantics/altIdentifier/doi/10.4161/auto.6.1.10698
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 Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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_ 1799194688661487616
spelling α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cellsMestre, María BelénFader Kaiser, Claudio MarceloSola, Claudia del ValleColombo, María IsabelAUTOPHAGYLC3STAPHYLOCOCCUS AUREUSTOXINΑ-HEMOLYSINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly leading to staphylococcal persistence and chronic disease. It has been previously shown that this pathogen localizes to LC3-labeled compartments and subverts the autophagy pathway. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. In the present report we present evidence that the pore-forming toxin α-hemolysin (hla) is a S. aureus secreted factor which participates in the activation of the autophagic pathway. In addition, our results indicate that although the toxin elicits an autophagic response this pathway is dysfunctional as indicated by the accumulation of the LC3-II form in cell lysates obtained from intoxicated cells. In addition, not only the purified hla toxin but also the toxin-secreting pathogen prevented the maturation of autophagosomes. Interestingly, in cells infected with the wild-type strain of S. aureus the bacteria-containing compartments which recruited LC3 onto the limiting membrane did not accumulate the acidotropic probe LysoTracker. In contrast, those phagosomes containing the hla(-) mutant (unable to produce the toxin) localized in an acidic compartment unlabeled by LC3. These results suggest that the LC3 protein is recruited only to those damaged vacuoles (i.e., perforated by the toxin), perhaps as an attempt to protect the cells. Furthermore, we have demonstrated that the toxin-dependent activation of autophagy (although it is regulated by calcium and requires Atg5) is independent of both PI3Kinase activity and Beclin 1 suggesting the involvement of a non-canonical autophagy pathway. © 2010 Landes Bioscience.Fil: Mestre, María Belén. 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; ArgentinaFil: Fader Kaiser, Claudio Marcelo. 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; ArgentinaFil: Sola, Claudia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Colombo, María 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; ArgentinaLandes Bioscience2010-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/189126Mestre, María Belén; Fader Kaiser, Claudio Marcelo; Sola, Claudia del Valle; Colombo, María Isabel; α-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells; Landes Bioscience; Autophagy; 6; 1; 1-2010; 110-1251554-86271554-8635CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/20110774/info:eu-repo/semantics/altIdentifier/doi/10.4161/auto.6.1.10698info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:34:15Zoai:ri.conicet.gov.ar:11336/189126instacron: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:34982024-05-08 13:34:15.787CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
score 15,812429

Similar Items