Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response

The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a...

Descripción completa

Detalles Bibliográficos
Autores: Ramos-Sevillano, Elisa, Urzainqui, Ana, Campuzano, Susana, Moscoso, Miriam, Gonzalez-Camacho, Fernando, Domenech Lucas, Mirian, Rodriguez de Cordoba, Santiago, Sánchez Madrid, Francisco, Brown, Jeremy S, García, Ernesto, Yuste, Jose Enrique
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8592
Acceso en línea:http://hdl.handle.net/20.500.12105/8592
Access Level:acceso abierto
Palabra clave:Animals
Bacterial Capsules
Bacterial Proteins
Cell Wall
Complement Activation
Complement C3
Complement Factor H
Histocompatibility Antigens
Host-Pathogen Interactions
Mice
Mice, Inbred C57BL
N-Acetylmuramoyl-L-alanine Amidase
Phagocytosis
Phosphorylcholine
Pneumococcal Infections
Polysaccharides, Bacterial
Sepsis
Streptococcus pneumoniae
Streptolysins
id ES_6f2adbe5b4bc89b742d0d72e2ccd78be
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/8592
network_acronym_str ES
network_name_str España
repository_id_str
spelling Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune responseRamos-Sevillano, ElisaUrzainqui, AnaCampuzano, SusanaMoscoso, MiriamGonzalez-Camacho, FernandoDomenech Lucas, MirianRodriguez de Cordoba, SantiagoSánchez Madrid, FranciscoBrown, Jeremy SGarcía, ErnestoYuste, Jose EnriqueAnimalsBacterial CapsulesBacterial ProteinsCell WallComplement ActivationComplement C3Complement Factor HHistocompatibility AntigensHost-Pathogen InteractionsMiceMice, Inbred C57BLN-Acetylmuramoyl-L-alanine AmidasePhagocytosisPhosphorylcholinePneumococcal InfectionsPolysaccharides, BacterialSepsisStreptococcus pneumoniaeStreptolysinsThe complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.American Society for Microbiology (ASM)Ministerio de Economía y Competitividad (España)Instituto de Salud Carlos III20192019-11-1420152015-02-0120152015-02-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/8592reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengSAF2012-39444-C01 02 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/85922026-06-12T12:43:37Z
dc.title.none.fl_str_mv Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
title Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
spellingShingle Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
Ramos-Sevillano, Elisa
Animals
Bacterial Capsules
Bacterial Proteins
Cell Wall
Complement Activation
Complement C3
Complement Factor H
Histocompatibility Antigens
Host-Pathogen Interactions
Mice
Mice, Inbred C57BL
N-Acetylmuramoyl-L-alanine Amidase
Phagocytosis
Phosphorylcholine
Pneumococcal Infections
Polysaccharides, Bacterial
Sepsis
Streptococcus pneumoniae
Streptolysins
title_short Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
title_full Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
title_fullStr Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
title_full_unstemmed Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
title_sort Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
dc.creator.none.fl_str_mv Ramos-Sevillano, Elisa
Urzainqui, Ana
Campuzano, Susana
Moscoso, Miriam
Gonzalez-Camacho, Fernando
Domenech Lucas, Mirian
Rodriguez de Cordoba, Santiago
Sánchez Madrid, Francisco
Brown, Jeremy S
García, Ernesto
Yuste, Jose Enrique
author Ramos-Sevillano, Elisa
author_facet Ramos-Sevillano, Elisa
Urzainqui, Ana
Campuzano, Susana
Moscoso, Miriam
Gonzalez-Camacho, Fernando
Domenech Lucas, Mirian
Rodriguez de Cordoba, Santiago
Sánchez Madrid, Francisco
Brown, Jeremy S
García, Ernesto
Yuste, Jose Enrique
author_role author
author2 Urzainqui, Ana
Campuzano, Susana
Moscoso, Miriam
Gonzalez-Camacho, Fernando
Domenech Lucas, Mirian
Rodriguez de Cordoba, Santiago
Sánchez Madrid, Francisco
Brown, Jeremy S
García, Ernesto
Yuste, Jose Enrique
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Animals
Bacterial Capsules
Bacterial Proteins
Cell Wall
Complement Activation
Complement C3
Complement Factor H
Histocompatibility Antigens
Host-Pathogen Interactions
Mice
Mice, Inbred C57BL
N-Acetylmuramoyl-L-alanine Amidase
Phagocytosis
Phosphorylcholine
Pneumococcal Infections
Polysaccharides, Bacterial
Sepsis
Streptococcus pneumoniae
Streptolysins
topic Animals
Bacterial Capsules
Bacterial Proteins
Cell Wall
Complement Activation
Complement C3
Complement Factor H
Histocompatibility Antigens
Host-Pathogen Interactions
Mice
Mice, Inbred C57BL
N-Acetylmuramoyl-L-alanine Amidase
Phagocytosis
Phosphorylcholine
Pneumococcal Infections
Polysaccharides, Bacterial
Sepsis
Streptococcus pneumoniae
Streptolysins
description The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-02-01
2015
2015-02-01
2019
2019-11-14
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/8592
url http://hdl.handle.net/20.500.12105/8592
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv SAF2012-39444-C01 02 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/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
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology (ASM)
publisher.none.fl_str_mv American Society for Microbiology (ASM)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410476430983168
score 15,811543

Similares en LA Referencia