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The Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatis

dc.contributor.authorPereira, Inês Serrano
dc.contributor.authorPais, Sara Vilela
dc.contributor.authorBorges, Vítor
dc.contributor.authorBorrego, Maria José
dc.contributor.authorGomes, João Paulo
dc.contributor.authorMota, Luís Jaime
dc.date.accessioned2023-01-31T12:02:09Z
dc.date.available2023-01-31T12:02:09Z
dc.date.issued2022-07-08
dc.description.abstractChlamydia 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.pt_PT
dc.description.sponsorshipThis 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Cell Infect Microbiol. 2022 Jul 8;12:902210. doi: 10.3389/fcimb.2022.902210. eCollection 2022.pt_PT
dc.identifier.doi10.3389/fcimb.2022.902210pt_PT
dc.identifier.issn2235-2988
dc.identifier.urihttp://hdl.handle.net/10400.18/8480
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Mediapt_PT
dc.relationApplied Molecular Biosciences Unit
dc.relationApplied Molecular Biosciences Unit
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fcimb.2022.902210/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectChlamydia trachomatispt_PT
dc.subjectEffectorspt_PT
dc.subjectHost-pathogen Interactionspt_PT
dc.subjectPathogen Egresspt_PT
dc.subjectType III Secretionpt_PT
dc.subjectInfecções Sexualmente Transmissíveispt_PT
dc.titleThe Type III Secretion Effector CteG Mediates Host Cell Lytic Exit of Chlamydia trachomatispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MIC%2F28503%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.citation.startPage902210pt_PT
oaire.citation.titleFrontiers in Cellular and Infection Microbiologypt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication4595549e-8089-4478-855e-9af8db9d1647
relation.isProjectOfPublicationf10335ba-6a11-4a72-b082-182ce09d548d
relation.isProjectOfPublicationb6e46a61-d241-4879-b841-169d21cd75b9
relation.isProjectOfPublication.latestForDiscovery4595549e-8089-4478-855e-9af8db9d1647

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