Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acu...

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Autores: Thofte, Oskar, Bettoni, Serena, Su, Yu Ching, Thegerström, John, Jonsson, Sandra, Mattsson, Emma, Sandblad, Linda, Martí Martí, Sara, Garmendia, Junkal, Blom, Anna M., Riesbeck, Kristian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182733
Acceso en línea:https://hdl.handle.net/2445/182733
Access Level:acceso abierto
Palabra clave:Bacils
Bacteris patògens
Proteïnes
Bacillus (Bacteria)
Pathogenic bacteria
Proteins
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spelling Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum ResistanceThofte, OskarBettoni, SerenaSu, Yu ChingThegerström, JohnJonsson, SandraMattsson, EmmaSandblad, LindaMartí Martí, SaraGarmendia, JunkalBlom, Anna M.Riesbeck, KristianBacilsBacteris patògensProteïnesBacillus (Bacteria)Pathogenic bacteriaProteinsNontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.The American Association of Immunologists2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/182733Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.4049/jimmunol.2100105The Journal of Immunology, 2021, vol 207, num 6, p. 1566-1577https://doi.org/10.4049/jimmunol.2100105cc by (c) Thofte, Oskar et al, 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1827332026-05-27T06:46:51Z
dc.title.none.fl_str_mv Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
title Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
spellingShingle Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
Thofte, Oskar
Bacils
Bacteris patògens
Proteïnes
Bacillus (Bacteria)
Pathogenic bacteria
Proteins
title_short Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
title_full Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
title_fullStr Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
title_full_unstemmed Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
title_sort Nontypeable Haemophilus influenzae P5 Binds Human C4b-Binding Protein, Promoting Serum Resistance
dc.creator.none.fl_str_mv Thofte, Oskar
Bettoni, Serena
Su, Yu Ching
Thegerström, John
Jonsson, Sandra
Mattsson, Emma
Sandblad, Linda
Martí Martí, Sara
Garmendia, Junkal
Blom, Anna M.
Riesbeck, Kristian
author Thofte, Oskar
author_facet Thofte, Oskar
Bettoni, Serena
Su, Yu Ching
Thegerström, John
Jonsson, Sandra
Mattsson, Emma
Sandblad, Linda
Martí Martí, Sara
Garmendia, Junkal
Blom, Anna M.
Riesbeck, Kristian
author_role author
author2 Bettoni, Serena
Su, Yu Ching
Thegerström, John
Jonsson, Sandra
Mattsson, Emma
Sandblad, Linda
Martí Martí, Sara
Garmendia, Junkal
Blom, Anna M.
Riesbeck, Kristian
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bacils
Bacteris patògens
Proteïnes
Bacillus (Bacteria)
Pathogenic bacteria
Proteins
topic Bacils
Bacteris patògens
Proteïnes
Bacillus (Bacteria)
Pathogenic bacteria
Proteins
description Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/2445/182733
url https://hdl.handle.net/2445/182733
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.4049/jimmunol.2100105
The Journal of Immunology, 2021, vol 207, num 6, p. 1566-1577
https://doi.org/10.4049/jimmunol.2100105
dc.rights.none.fl_str_mv cc by (c) Thofte, Oskar et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Thofte, Oskar et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv The American Association of Immunologists
publisher.none.fl_str_mv The American Association of Immunologists
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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