The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/8480 |
Resumo: | Chlamydia trachomatis is an obligate intracellular bacterium causing ocular and urogenital infections in humans that are a significant burden worldwide. The completion of its characteristic infectious cycle relies on the manipulation of several host cell processes by numerous chlamydial type III secretion effector proteins. We previously identified the C. trachomatis CteG effector and showed it localizes at the host cell plasma membrane at late stages of infection. Here, we showed that, from 48 h post-infection, mammalian cells infected by wild-type C. trachomatis contained more infectious chlamydiae in the culture supernatant than cells infected by a CteG-deficient strain. This phenotype was CteG-dependent as it could be complemented in cells infected by the CteG-deficient strain carrying a plasmid encoding CteG. Furthermore, we detected a CteG-dependent defect on host cell cytotoxicity, indicating that CteG mediates chlamydial lytic exit. Previous studies showed that Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, also mediates chlamydial lytic exit. However, by using C. trachomatis strains encoding or lacking Pgp4, we showed that production and localization of CteG are not regulated by Pgp4. A C. trachomatis strain lacking both CteG and Pgp4 was as defective in promoting host cell cytotoxicity as mutant strains lacking only CteG or Pgp4. Furthermore, CteG overproduction in a plasmid suppressed the host cell cytotoxic defect of CteG- and Pgp4-deficient chlamydiae. Overall, we revealed the first chlamydial type III secretion effector involved in host cell lytic exit. Our data indicates that CteG and Pgp4 participate in a single cascade of events, but involving multiple layers of regulation, leading to lysis of host cells and release of the infectious chlamydiae. |
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The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatisChlamydia trachomatisEffectorsHost-pathogen InteractionsPathogen EgressType III SecretionInfecções Sexualmente TransmissíveisChlamydia trachomatis is an obligate intracellular bacterium causing ocular and urogenital infections in humans that are a significant burden worldwide. The completion of its characteristic infectious cycle relies on the manipulation of several host cell processes by numerous chlamydial type III secretion effector proteins. We previously identified the C. trachomatis CteG effector and showed it localizes at the host cell plasma membrane at late stages of infection. Here, we showed that, from 48 h post-infection, mammalian cells infected by wild-type C. trachomatis contained more infectious chlamydiae in the culture supernatant than cells infected by a CteG-deficient strain. This phenotype was CteG-dependent as it could be complemented in cells infected by the CteG-deficient strain carrying a plasmid encoding CteG. Furthermore, we detected a CteG-dependent defect on host cell cytotoxicity, indicating that CteG mediates chlamydial lytic exit. Previous studies showed that Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, also mediates chlamydial lytic exit. However, by using C. trachomatis strains encoding or lacking Pgp4, we showed that production and localization of CteG are not regulated by Pgp4. A C. trachomatis strain lacking both CteG and Pgp4 was as defective in promoting host cell cytotoxicity as mutant strains lacking only CteG or Pgp4. Furthermore, CteG overproduction in a plasmid suppressed the host cell cytotoxic defect of CteG- and Pgp4-deficient chlamydiae. Overall, we revealed the first chlamydial type III secretion effector involved in host cell lytic exit. Our data indicates that CteG and Pgp4 participate in a single cascade of events, but involving multiple layers of regulation, leading to lysis of host cells and release of the infectious chlamydiae.This work was supported by Fundação para a Ciência e Tecnologia (FCT) through grant PTDC/BIA-MIC/28503/2017, and in the scope of the projects UIDP/04378/2020 and UIDB/ 04378/2020 of the Research Unit on Applied Molecular Biosciences – UCIBIO, and LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. ISP and SVP were supported by PhD fellowships SFRH/BD/129756/2017 and PD/BD/52210/2013, respectively, also funded by FCT. SVP PhD fellowship was within the scope of the PhD program Molecular Biosciences (PD/00133/2012), funded by FCT.Frontiers MediaRepositório Científico do Instituto Nacional de SaúdePereira, Inês SerranoPais, Sara VilelaBorges, VítorBorrego, Maria JoséGomes, João PauloMota, Luís Jaime2023-01-31T12:02:09Z2022-07-082022-07-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8480engFront Cell Infect Microbiol. 2022 Jul 8;12:902210. doi: 10.3389/fcimb.2022.902210. eCollection 2022.2235-298810.3389/fcimb.2022.902210info: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:RCAAP2023-07-20T15:42:35Zoai:repositorio.insa.pt:10400.18/8480Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:43:06.529866Repositório 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 |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
title |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
spellingShingle |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis Pereira, Inês Serrano Chlamydia trachomatis Effectors Host-pathogen Interactions Pathogen Egress Type III Secretion Infecções Sexualmente Transmissíveis |
title_short |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
title_full |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
title_fullStr |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
title_full_unstemmed |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
title_sort |
The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis |
author |
Pereira, Inês Serrano |
author_facet |
Pereira, Inês Serrano Pais, Sara Vilela Borges, Vítor Borrego, Maria José Gomes, João Paulo Mota, Luís Jaime |
author_role |
author |
author2 |
Pais, Sara Vilela Borges, Vítor Borrego, Maria José Gomes, João Paulo Mota, Luís Jaime |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Pereira, Inês Serrano Pais, Sara Vilela Borges, Vítor Borrego, Maria José Gomes, João Paulo Mota, Luís Jaime |
dc.subject.por.fl_str_mv |
Chlamydia trachomatis Effectors Host-pathogen Interactions Pathogen Egress Type III Secretion Infecções Sexualmente Transmissíveis |
topic |
Chlamydia trachomatis Effectors Host-pathogen Interactions Pathogen Egress Type III Secretion Infecções Sexualmente Transmissíveis |
description |
Chlamydia trachomatis is an obligate intracellular bacterium causing ocular and urogenital infections in humans that are a significant burden worldwide. The completion of its characteristic infectious cycle relies on the manipulation of several host cell processes by numerous chlamydial type III secretion effector proteins. We previously identified the C. trachomatis CteG effector and showed it localizes at the host cell plasma membrane at late stages of infection. Here, we showed that, from 48 h post-infection, mammalian cells infected by wild-type C. trachomatis contained more infectious chlamydiae in the culture supernatant than cells infected by a CteG-deficient strain. This phenotype was CteG-dependent as it could be complemented in cells infected by the CteG-deficient strain carrying a plasmid encoding CteG. Furthermore, we detected a CteG-dependent defect on host cell cytotoxicity, indicating that CteG mediates chlamydial lytic exit. Previous studies showed that Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, also mediates chlamydial lytic exit. However, by using C. trachomatis strains encoding or lacking Pgp4, we showed that production and localization of CteG are not regulated by Pgp4. A C. trachomatis strain lacking both CteG and Pgp4 was as defective in promoting host cell cytotoxicity as mutant strains lacking only CteG or Pgp4. Furthermore, CteG overproduction in a plasmid suppressed the host cell cytotoxic defect of CteG- and Pgp4-deficient chlamydiae. Overall, we revealed the first chlamydial type III secretion effector involved in host cell lytic exit. Our data indicates that CteG and Pgp4 participate in a single cascade of events, but involving multiple layers of regulation, leading to lysis of host cells and release of the infectious chlamydiae. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-07-08 2022-07-08T00:00:00Z 2023-01-31T12:02:09Z |
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/10400.18/8480 |
url |
http://hdl.handle.net/10400.18/8480 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Front Cell Infect Microbiol. 2022 Jul 8;12:902210. doi: 10.3389/fcimb.2022.902210. eCollection 2022. 2235-2988 10.3389/fcimb.2022.902210 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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