Factor H-related protein 1 promotes complement-mediated opsonization of .

Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator tha...

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Autores: Gonzalez-Alsina, Alex, Martín-Merinero, Héctor, Mateu-Borrás, Margalida, Verd, María, Doménech-Sánchez, Antonio, Goldberg, Joanna B, Rodríguez de Córdoba, Santiago, Alberti, Sebastian
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/24958
Acceso en línea:https://hdl.handle.net/20.500.13003/24958
Access Level:acceso abierto
Palabra clave:Pseudomonas aeruginosa
Complement Factor H
Factor H de Complemento
FHR-1
OprG
P. aeruginosa
complement system
factor H
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spelling Factor H-related protein 1 promotes complement-mediated opsonization of .Gonzalez-Alsina, AlexMartín-Merinero, HéctorMateu-Borrás, MargalidaVerd, MaríaDoménech-Sánchez, AntonioGoldberg, Joanna BRodríguez de Córdoba, SantiagoAlberti, SebastianPseudomonas aeruginosaComplement Factor HPseudomonas aeruginosaFactor H de ComplementoFHR-1OprGP. aeruginosacomplement systemfactor HPseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator that inactivates C3b, preventing the formation of the C3-convertase and complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere in this bacterial mechanism of resisting complement. Here, we show that FHR-1 binds to P. aeruginosa via the outer membrane protein OprG in a lipopolysaccharide (LPS) O antigen-dependent manner. Binding assays with purified components or with FHR-1-deficient serum supplemented with FHR-1 show that FHR-1 competes with FH for binding to P. aeruginosa. Blockage of FH binding to C3b deposited on the bacteria reduces FH-mediated cofactor activity of C3b degradation, increasing the opsonization of the bacteria and the formation of the potent chemoattractant C5a. Overall, our findings indicate that FHR-1 is a host factor that promotes complement activation, facilitating clearance of P. aeruginosa by opsonophagocytosis.Frontiers20242024-01-0120242024-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/24958reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/249582026-06-22T12:44:07Z
dc.title.none.fl_str_mv Factor H-related protein 1 promotes complement-mediated opsonization of .
title Factor H-related protein 1 promotes complement-mediated opsonization of .
spellingShingle Factor H-related protein 1 promotes complement-mediated opsonization of .
Gonzalez-Alsina, Alex
Pseudomonas aeruginosa
Complement Factor H
Pseudomonas aeruginosa
Factor H de Complemento
FHR-1
OprG
P. aeruginosa
complement system
factor H
title_short Factor H-related protein 1 promotes complement-mediated opsonization of .
title_full Factor H-related protein 1 promotes complement-mediated opsonization of .
title_fullStr Factor H-related protein 1 promotes complement-mediated opsonization of .
title_full_unstemmed Factor H-related protein 1 promotes complement-mediated opsonization of .
title_sort Factor H-related protein 1 promotes complement-mediated opsonization of .
dc.creator.none.fl_str_mv Gonzalez-Alsina, Alex
Martín-Merinero, Héctor
Mateu-Borrás, Margalida
Verd, María
Doménech-Sánchez, Antonio
Goldberg, Joanna B
Rodríguez de Córdoba, Santiago
Alberti, Sebastian
author Gonzalez-Alsina, Alex
author_facet Gonzalez-Alsina, Alex
Martín-Merinero, Héctor
Mateu-Borrás, Margalida
Verd, María
Doménech-Sánchez, Antonio
Goldberg, Joanna B
Rodríguez de Córdoba, Santiago
Alberti, Sebastian
author_role author
author2 Martín-Merinero, Héctor
Mateu-Borrás, Margalida
Verd, María
Doménech-Sánchez, Antonio
Goldberg, Joanna B
Rodríguez de Córdoba, Santiago
Alberti, Sebastian
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Pseudomonas aeruginosa
Complement Factor H
Pseudomonas aeruginosa
Factor H de Complemento
FHR-1
OprG
P. aeruginosa
complement system
factor H
topic Pseudomonas aeruginosa
Complement Factor H
Pseudomonas aeruginosa
Factor H de Complemento
FHR-1
OprG
P. aeruginosa
complement system
factor H
description Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator that inactivates C3b, preventing the formation of the C3-convertase and complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere in this bacterial mechanism of resisting complement. Here, we show that FHR-1 binds to P. aeruginosa via the outer membrane protein OprG in a lipopolysaccharide (LPS) O antigen-dependent manner. Binding assays with purified components or with FHR-1-deficient serum supplemented with FHR-1 show that FHR-1 competes with FH for binding to P. aeruginosa. Blockage of FH binding to C3b deposited on the bacteria reduces FH-mediated cofactor activity of C3b degradation, increasing the opsonization of the bacteria and the formation of the potent chemoattractant C5a. Overall, our findings indicate that FHR-1 is a host factor that promotes complement activation, facilitating clearance of P. aeruginosa by opsonophagocytosis.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/24958
url https://hdl.handle.net/20.500.13003/24958
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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