A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector

Detalhes bibliográficos
Autor(a) principal: Monteiro, Inês P.
Data de Publicação: 2022
Outros Autores: Sousa, Sofia, Borges, Vítor, Gonçalves, Paulo, Gomes, João Paulo, Mota, Luís Jaime, Franco, Irina S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/143190
Resumo: LA/P/0140/2020
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spelling A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic EffectorhomologIcm/Dot effectorsinfectionLegionella pneumophilanucleomodulinoutbreak straintype 4 secretion system (T4SS)MicrobiologyImmunologyMicrobiology (medical)Infectious DiseasesSDG 3 - Good Health and Well-beingLA/P/0140/2020Legionella pneumophila is an accidental human pathogen that causes the potentially fatal Legionnaires’ disease, a severe type of pneumonia. The main virulence mechanism of L. pneumophila is a Type 4B Secretion System (T4SS) named Icm/Dot that transports effector proteins into the host cell cytosol. The concerted action of effectors on several host cell processes leads to the formation of an intracellular Legionella-containing vacuole that is replication competent and avoids phagolysosomal degradation. To date over 300 Icm/Dot substrates have been identified. In this study, we searched the genome of a L. pneumophila strain (Pt/VFX2014) responsible for the second largest L. pneumophila outbreak worldwide (in Vila Franca de Xira, Portugal, in 2014) for genes encoding potential novel Icm/Dot substrates. This strain Pt/VFX2014 belongs to serogroup 1 but phylogenetically segregates from all other serogroup 1 strains previously sequenced, displaying a unique mosaic genetic backbone. The ability of the selected putative effectors to be delivered into host cells by the T4SS was confirmed using the TEM-1 β-lactamase reporter assay. Two previously unknown Icm/Dot effectors were identified, VFX05045 and VFX10045, whose homologs Lpp1450 and Lpp3070 in clinical strain L. pneumophila Paris were also confirmed as T4SS substrates. After delivery into the host cell cytosol, homologs VFX05045/Lpp1450 remained diffused in the cell, similarly to Lpp3070. In contrast, VFX10045 localized to the host cell nucleus. To understand how VFX10045 and Lpp3070 (94% of identity at amino acid level) are directed to distinct sites, we carried out a comprehensive site-directed mutagenesis followed by analyses of the subcellular localization of the mutant proteins. This led to the delineation of region in the C-terminal part (residues 380 to 534) of the 583 amino acid-long VFX10045 as necessary and sufficient for nuclear targeting and highlighted the fundamental function of the VFX10045-specific R440 and I441 residues in this process. These studies revealed a strain-specific nucleotropism for new effector VFX10045/Lpp3070, which anticipates distinct functions between these homologs.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNMonteiro, Inês P.Sousa, SofiaBorges, VítorGonçalves, PauloGomes, João PauloMota, Luís JaimeFranco, Irina S.2022-08-22T22:16:43Z2022-05-312022-05-31T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/143190eng2235-2988PURE: 45348550https://doi.org/10.3389/fcimb.2022.864626info: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:RCAAP2024-03-11T05:21:22Zoai:run.unl.pt:10362/143190Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:50:44.898995Repositório 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 A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
title A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
spellingShingle A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
Monteiro, Inês P.
homolog
Icm/Dot effectors
infection
Legionella pneumophila
nucleomodulin
outbreak strain
type 4 secretion system (T4SS)
Microbiology
Immunology
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
title_short A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
title_full A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
title_fullStr A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
title_full_unstemmed A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
title_sort A Search for Novel Legionella pneumophila Effector Proteins Reveals a Strain Specific Nucleotropic Effector
author Monteiro, Inês P.
author_facet Monteiro, Inês P.
Sousa, Sofia
Borges, Vítor
Gonçalves, Paulo
Gomes, João Paulo
Mota, Luís Jaime
Franco, Irina S.
author_role author
author2 Sousa, Sofia
Borges, Vítor
Gonçalves, Paulo
Gomes, João Paulo
Mota, Luís Jaime
Franco, Irina S.
author2_role 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 Monteiro, Inês P.
Sousa, Sofia
Borges, Vítor
Gonçalves, Paulo
Gomes, João Paulo
Mota, Luís Jaime
Franco, Irina S.
dc.subject.por.fl_str_mv homolog
Icm/Dot effectors
infection
Legionella pneumophila
nucleomodulin
outbreak strain
type 4 secretion system (T4SS)
Microbiology
Immunology
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
topic homolog
Icm/Dot effectors
infection
Legionella pneumophila
nucleomodulin
outbreak strain
type 4 secretion system (T4SS)
Microbiology
Immunology
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
description LA/P/0140/2020
publishDate 2022
dc.date.none.fl_str_mv 2022-08-22T22:16:43Z
2022-05-31
2022-05-31T00:00:00Z
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/10362/143190
url http://hdl.handle.net/10362/143190
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2235-2988
PURE: 45348550
https://doi.org/10.3389/fcimb.2022.864626
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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