Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells

Detalhes bibliográficos
Autor(a) principal: Varon, C.
Data de Publicação: 2014
Outros Autores: Mocan, I., Mihi, B., Péré-Védrenne, C., Aboubacar, A., Moraté, C., Oleastro, M., Doignon, F., Laharie, D., Mégraud, F., Ménard, A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/2922
Resumo: Helicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.
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spelling Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cellsHelicobacter pullorumActinAdherenceCortactinCytolethal Distending ToxinEpithelial CellsIsogenic MutantLamellipodiaLentivirusVinculinInfecções GastrointestinaisHelicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.This work was supported by the Institut national de la santé et de la recherche médicale, the University Bordeaux Segalen, the Conseil Régional d’Aquitaine (grants 20030304002FA and 20040305003 FA), the Société Nationale Française de Gastroentérologie, the European Union (FEDER no. 2003227)Oxford University Press/Infectious Diseases Society of AmericaRepositório Científico do Instituto Nacional de SaúdeVaron, C.Mocan, I.Mihi, B.Péré-Védrenne, C.Aboubacar, A.Moraté, C.Oleastro, M.Doignon, F.Laharie, D.Mégraud, F.Ménard, A.2015-02-19T13:53:17Z2014-02-152014-02-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/2922engJ Infect Dis. 2014 Feb 15;209(4):588-99. doi: 10.1093/infdis/jit5390022-189910.1093/infdis/jit539info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:39:21Zoai:repositorio.insa.pt:10400.18/2922Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:37:33.671145Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
title Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
spellingShingle Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
Varon, C.
Helicobacter pullorum
Actin
Adherence
Cortactin
Cytolethal Distending Toxin
Epithelial Cells
Isogenic Mutant
Lamellipodia
Lentivirus
Vinculin
Infecções Gastrointestinais
title_short Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
title_full Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
title_fullStr Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
title_full_unstemmed Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
title_sort Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
author Varon, C.
author_facet Varon, C.
Mocan, I.
Mihi, B.
Péré-Védrenne, C.
Aboubacar, A.
Moraté, C.
Oleastro, M.
Doignon, F.
Laharie, D.
Mégraud, F.
Ménard, A.
author_role author
author2 Mocan, I.
Mihi, B.
Péré-Védrenne, C.
Aboubacar, A.
Moraté, C.
Oleastro, M.
Doignon, F.
Laharie, D.
Mégraud, F.
Ménard, A.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Varon, C.
Mocan, I.
Mihi, B.
Péré-Védrenne, C.
Aboubacar, A.
Moraté, C.
Oleastro, M.
Doignon, F.
Laharie, D.
Mégraud, F.
Ménard, A.
dc.subject.por.fl_str_mv Helicobacter pullorum
Actin
Adherence
Cortactin
Cytolethal Distending Toxin
Epithelial Cells
Isogenic Mutant
Lamellipodia
Lentivirus
Vinculin
Infecções Gastrointestinais
topic Helicobacter pullorum
Actin
Adherence
Cortactin
Cytolethal Distending Toxin
Epithelial Cells
Isogenic Mutant
Lamellipodia
Lentivirus
Vinculin
Infecções Gastrointestinais
description Helicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.
publishDate 2014
dc.date.none.fl_str_mv 2014-02-15
2014-02-15T00:00:00Z
2015-02-19T13:53:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/2922
url http://hdl.handle.net/10400.18/2922
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Infect Dis. 2014 Feb 15;209(4):588-99. doi: 10.1093/infdis/jit539
0022-1899
10.1093/infdis/jit539
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press/Infectious Diseases Society of America
publisher.none.fl_str_mv Oxford University Press/Infectious Diseases Society of America
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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