Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors
| Autor(a) principal: | |
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| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://doi.org/10.1371/journal.pone.0133420 |
Resumo: | Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BD/68527/2010); Wellcome Trust ISSF grant (097831/Z/11/Z); FCT (SFRH/BD/68532/2010; SFRH/BPD/75295/2010) |
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Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factorsOBLIGATE INTRACELLULAR PATHOGENGUANYLATE BINDING-PROTEINSIII SECRETION MECHANISMEARLY-CYCLE DEVELOPMENTOUTER-MEMBRANE COMPLEXHISTONE-LIKE PROTEINMESSENGER-RNA DECAYKAPPA-B PATHWAYLYMPHOGRANULOMA-VENEREUMESCHERICHIA-COLIAgricultural and Biological Sciences(all)Biochemistry, Genetics and Molecular Biology(all)Medicine(all)Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BD/68527/2010); Wellcome Trust ISSF grant (097831/Z/11/Z); FCT (SFRH/BD/68532/2010; SFRH/BPD/75295/2010)Research on the obligate intracellular bacterium Chlamydia trachomatis demands culture in cell-lines, but the adaptive process behind the in vivo to in vitro transition is not understood. We assessed the genomic and transcriptomic dynamics underlying C.Trachomatis in vitro adaptation of strains representing the three disease groups (ocular, epithelial-genital and lymphogranuloma venereum) propagated in epithelial cells over multiple passages.We found genetic features potentially underlying phase variation mechanisms mediating the regulation of a lipid A biosynthesis enzyme (CT533/LpxC), and the functionality of the cytotoxin (CT166) through an ON/OFF mechanism. We detected inactivating mutations in CT713/porB, a scenario suggesting metabolic adaptation to the available carbon source. CT135 was inactivated in a tropism-specific manner, with CT135-negative clones emerging for all epithelial-genital populations (but not for LGV and ocular populations) and rapidly increasing in frequency (~23%mutants per10 passages). RNA-sequencing analyses revealed that a deletion event involving CT135 impacted the expression of multiple virulence factors, namely effectors known to play a role in the C.Trachomatis host-cell invasion or subversion (e.g., CT456/Tarp, CT694, CT875/TepP and CT868/ChlaDub1). This reflects a scenario of attenuation of C.Trachomatis virulence in vitro, which may take place independently or in a cumulative fashion with the also observed down-regulation of plasmid-related virulence factors. This issue may be relevant on behalf of the recent advances in Chlamydia mutagenesis and transformation where culture propagation for selecting mutants/transformants is mandatory. Finally, there was an increase in the growth rate for all strains, reflecting gradual fitness enhancement over time. In general, these data shed light on the adaptive process underlying the C.Trachomatis in vivo to in vitro transition, and indicates that it would be prudent to restrict culture propagation to minimal passages and check the status of the CT135 genotype in order to avoid the selection of CT135-negative mutants, likely originating less virulent strains.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNBorges, VítorPinheiro, MiguelAntelo, MiniaSampaio, Daniel A.Vieira, LuísFerreira, RitaNunes, AlexandraAlmeida, FilipeMota, Luís J.Borrego, Maria J.Gomes, João Paulo2017-05-30T13:58:23Z2015-07-242015-07-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1371/journal.pone.0133420eng1932-6203PURE: 1217638http://www.scopus.com/inward/record.url?scp=84941712082&partnerID=8YFLogxKhttps://doi.org/10.1371/journal.pone.0133420info: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:RCAAP2024-03-11T04:06:41Zoai:run.unl.pt:10362/20809Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:29.544694Repositório 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 |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| title |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| spellingShingle |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors Borges, Vítor OBLIGATE INTRACELLULAR PATHOGEN GUANYLATE BINDING-PROTEINS III SECRETION MECHANISM EARLY-CYCLE DEVELOPMENT OUTER-MEMBRANE COMPLEX HISTONE-LIKE PROTEIN MESSENGER-RNA DECAY KAPPA-B PATHWAY LYMPHOGRANULOMA-VENEREUM ESCHERICHIA-COLI Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) |
| title_short |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| title_full |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| title_fullStr |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| title_full_unstemmed |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| title_sort |
Chlamydia Trachomatis in vivo to in vitro transition reveals mechanisms of phase variation and down-regulation of virulence factors |
| author |
Borges, Vítor |
| author_facet |
Borges, Vítor Pinheiro, Miguel Antelo, Minia Sampaio, Daniel A. Vieira, Luís Ferreira, Rita Nunes, Alexandra Almeida, Filipe Mota, Luís J. Borrego, Maria J. Gomes, João Paulo |
| author_role |
author |
| author2 |
Pinheiro, Miguel Antelo, Minia Sampaio, Daniel A. Vieira, Luís Ferreira, Rita Nunes, Alexandra Almeida, Filipe Mota, Luís J. Borrego, Maria J. Gomes, João Paulo |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit RUN |
| dc.contributor.author.fl_str_mv |
Borges, Vítor Pinheiro, Miguel Antelo, Minia Sampaio, Daniel A. Vieira, Luís Ferreira, Rita Nunes, Alexandra Almeida, Filipe Mota, Luís J. Borrego, Maria J. Gomes, João Paulo |
| dc.subject.por.fl_str_mv |
OBLIGATE INTRACELLULAR PATHOGEN GUANYLATE BINDING-PROTEINS III SECRETION MECHANISM EARLY-CYCLE DEVELOPMENT OUTER-MEMBRANE COMPLEX HISTONE-LIKE PROTEIN MESSENGER-RNA DECAY KAPPA-B PATHWAY LYMPHOGRANULOMA-VENEREUM ESCHERICHIA-COLI Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) |
| topic |
OBLIGATE INTRACELLULAR PATHOGEN GUANYLATE BINDING-PROTEINS III SECRETION MECHANISM EARLY-CYCLE DEVELOPMENT OUTER-MEMBRANE COMPLEX HISTONE-LIKE PROTEIN MESSENGER-RNA DECAY KAPPA-B PATHWAY LYMPHOGRANULOMA-VENEREUM ESCHERICHIA-COLI Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) |
| description |
Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BD/68527/2010); Wellcome Trust ISSF grant (097831/Z/11/Z); FCT (SFRH/BD/68532/2010; SFRH/BPD/75295/2010) |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-07-24 2015-07-24T00:00:00Z 2017-05-30T13:58:23Z |
| 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 |
https://doi.org/10.1371/journal.pone.0133420 |
| url |
https://doi.org/10.1371/journal.pone.0133420 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1932-6203 PURE: 1217638 http://www.scopus.com/inward/record.url?scp=84941712082&partnerID=8YFLogxK https://doi.org/10.1371/journal.pone.0133420 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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