Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages

Detalhes bibliográficos
Autor(a) principal: Assis, Patricia A.
Data de Publicação: 2014
Outros Autores: Espindola, Milena S., Paula-Silva, Francisco W. G., Rios, Wendy M., Pereira, Priscilla A. T., Leao, Sylvia Cardoso [UNIFESP], Silva, Celio L., Faccioli, Lucia H.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000v0j5
Texto Completo: http://dx.doi.org/10.1186/1471-2180-14-128
http://repositorio.unifesp.br/handle/11600/37773
Resumo: Background: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production.
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spelling Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophagesMycobacteriumLipid mediatorPhospholipase CCell deathMacrophage necrosisProstaglandinsBackground: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production.Univ São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Bioquim & Imunol, BR-14040903 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2009/07169-5FAPESP: 2011/01845-9Biomed Central LtdUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Assis, Patricia A.Espindola, Milena S.Paula-Silva, Francisco W. G.Rios, Wendy M.Pereira, Priscilla A. T.Leao, Sylvia Cardoso [UNIFESP]Silva, Celio L.Faccioli, Lucia H.2016-01-24T14:37:18Z2016-01-24T14:37:18Z2014-05-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10application/pdfhttp://dx.doi.org/10.1186/1471-2180-14-128Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014.10.1186/1471-2180-14-128WOS000338156500001.pdf1471-2180http://repositorio.unifesp.br/handle/11600/37773WOS:000338156500001ark:/48912/001300000v0j5engBmc Microbiologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-08T09:15:51Zoai:repositorio.unifesp.br/:11600/37773Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:38:29.509057Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
title Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
spellingShingle Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
Assis, Patricia A.
Mycobacterium
Lipid mediator
Phospholipase C
Cell death
Macrophage necrosis
Prostaglandins
title_short Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
title_full Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
title_fullStr Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
title_full_unstemmed Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
title_sort Mycobacterium tuberculosis expressing phospholipase C subverts PGE(2) synthesis and induces necrosis in alveolar macrophages
author Assis, Patricia A.
author_facet Assis, Patricia A.
Espindola, Milena S.
Paula-Silva, Francisco W. G.
Rios, Wendy M.
Pereira, Priscilla A. T.
Leao, Sylvia Cardoso [UNIFESP]
Silva, Celio L.
Faccioli, Lucia H.
author_role author
author2 Espindola, Milena S.
Paula-Silva, Francisco W. G.
Rios, Wendy M.
Pereira, Priscilla A. T.
Leao, Sylvia Cardoso [UNIFESP]
Silva, Celio L.
Faccioli, Lucia H.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Assis, Patricia A.
Espindola, Milena S.
Paula-Silva, Francisco W. G.
Rios, Wendy M.
Pereira, Priscilla A. T.
Leao, Sylvia Cardoso [UNIFESP]
Silva, Celio L.
Faccioli, Lucia H.
dc.subject.por.fl_str_mv Mycobacterium
Lipid mediator
Phospholipase C
Cell death
Macrophage necrosis
Prostaglandins
topic Mycobacterium
Lipid mediator
Phospholipase C
Cell death
Macrophage necrosis
Prostaglandins
description Background: Phospholipases C (PLCs) are virulence factors found in several bacteria. in Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE(2), an essential factor in cell membrane protection.Results: Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. the isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE(2) production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE(2) inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE(2) production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.Conclusions: Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE(2) production.
publishDate 2014
dc.date.none.fl_str_mv 2014-05-19
2016-01-24T14:37:18Z
2016-01-24T14:37:18Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/1471-2180-14-128
Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014.
10.1186/1471-2180-14-128
WOS000338156500001.pdf
1471-2180
http://repositorio.unifesp.br/handle/11600/37773
WOS:000338156500001
dc.identifier.dark.fl_str_mv ark:/48912/001300000v0j5
url http://dx.doi.org/10.1186/1471-2180-14-128
http://repositorio.unifesp.br/handle/11600/37773
identifier_str_mv Bmc Microbiology. London: Biomed Central Ltd, v. 14, 10 p., 2014.
10.1186/1471-2180-14-128
WOS000338156500001.pdf
1471-2180
WOS:000338156500001
ark:/48912/001300000v0j5
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Bmc Microbiology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10
application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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