Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation

The peptidyl-prolyl-cis/trans-isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires’ disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagell...

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Detalhes bibliográficos
Autores: Karagöz, Mustafa Safa, Ünal, Can Murat, Mayer, Benjamin E., Müsken, Mathias, Borrero de Acuña, José Manuel, Steinert, Michael
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/156286
Acesso em linha:https://hdl.handle.net/11441/156286
https://doi.org/10.1128/iai.00276-22
Access Level:Acceso aberto
Palavra-chave:Flagella
Interactomics
Legionella pneumophila
Macrophage infectivity potentiator (Mip)
Peptidyl-prolyl cis/trans isomerase (PPIase)
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spelling Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes FlagellationKaragöz, Mustafa SafaÜnal, Can MuratMayer, Benjamin E.Müsken, MathiasBorrero de Acuña, José ManuelSteinert, MichaelFlagellaInteractomicsLegionella pneumophilaMacrophage infectivity potentiator (Mip)Peptidyl-prolyl cis/trans isomerase (PPIase)The peptidyl-prolyl-cis/trans-isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires’ disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagellin FlaA as bacterial interaction partners of Mip. The macrolide FK506, which inhibits the PPIase activity of Mip, interfered with the binding of Lpc2061. Moreover, we demonstrated that the N-terminal dimerization region and amino acid Y185 in the C-terminal PPIase domain of Mip are required for the binding of Lpc2061 and FlaA. The modeling of the interaction partners and global docking with Mip suggested nonoverlapping binding interfaces, and a molecular dynamic simulation predicted an increased stability for the tripartite interaction of Lpc2061, Mip, and FlaA. On the functional level, we demonstrated that Mip promotes L. pneumophila flagellation, which is positively influenced by the binding of Lpc2061 and reduced by FK506. Also, L. pneumophila mutants expressing the Y185A or the monomeric Mip variant, which bind less Lpc2061, were nonmotile, were less flagellated, and yielded less FlaA when quantified. To our knowledge, this is the first report in which a PPIase and its bacterial interaction partners were demonstrated to influence flagellation.Bundesministerium für Bildung und Forschung (BMBF) 16GW0213American Society for MicrobiologyMicrobiologíaBundesministerium für Bildung und Forschung (BMBF)2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/156286https://doi.org/10.1128/iai.00276-22reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInfection and Immunity, 90 (11), e0027622.16GW0213https://doi.org/10.1128/iai.00276-22info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1562862026-06-17T12:51:07Z
dc.title.none.fl_str_mv Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
title Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
spellingShingle Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
Karagöz, Mustafa Safa
Flagella
Interactomics
Legionella pneumophila
Macrophage infectivity potentiator (Mip)
Peptidyl-prolyl cis/trans isomerase (PPIase)
title_short Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
title_full Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
title_fullStr Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
title_full_unstemmed Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
title_sort Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation
dc.creator.none.fl_str_mv Karagöz, Mustafa Safa
Ünal, Can Murat
Mayer, Benjamin E.
Müsken, Mathias
Borrero de Acuña, José Manuel
Steinert, Michael
author Karagöz, Mustafa Safa
author_facet Karagöz, Mustafa Safa
Ünal, Can Murat
Mayer, Benjamin E.
Müsken, Mathias
Borrero de Acuña, José Manuel
Steinert, Michael
author_role author
author2 Ünal, Can Murat
Mayer, Benjamin E.
Müsken, Mathias
Borrero de Acuña, José Manuel
Steinert, Michael
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Microbiología
Bundesministerium für Bildung und Forschung (BMBF)
dc.subject.none.fl_str_mv Flagella
Interactomics
Legionella pneumophila
Macrophage infectivity potentiator (Mip)
Peptidyl-prolyl cis/trans isomerase (PPIase)
topic Flagella
Interactomics
Legionella pneumophila
Macrophage infectivity potentiator (Mip)
Peptidyl-prolyl cis/trans isomerase (PPIase)
description The peptidyl-prolyl-cis/trans-isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires’ disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagellin FlaA as bacterial interaction partners of Mip. The macrolide FK506, which inhibits the PPIase activity of Mip, interfered with the binding of Lpc2061. Moreover, we demonstrated that the N-terminal dimerization region and amino acid Y185 in the C-terminal PPIase domain of Mip are required for the binding of Lpc2061 and FlaA. The modeling of the interaction partners and global docking with Mip suggested nonoverlapping binding interfaces, and a molecular dynamic simulation predicted an increased stability for the tripartite interaction of Lpc2061, Mip, and FlaA. On the functional level, we demonstrated that Mip promotes L. pneumophila flagellation, which is positively influenced by the binding of Lpc2061 and reduced by FK506. Also, L. pneumophila mutants expressing the Y185A or the monomeric Mip variant, which bind less Lpc2061, were nonmotile, were less flagellated, and yielded less FlaA when quantified. To our knowledge, this is the first report in which a PPIase and its bacterial interaction partners were demonstrated to influence flagellation.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/156286
https://doi.org/10.1128/iai.00276-22
url https://hdl.handle.net/11441/156286
https://doi.org/10.1128/iai.00276-22
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Infection and Immunity, 90 (11), e0027622.
16GW0213
https://doi.org/10.1128/iai.00276-22
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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