Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo

Autores
Cools, F.; Torfs, E.; Vanhoutte, B.; Bidart De Macedo, M.; Bonofiglio, Laura; Mollerach, Marta Eugenia; Maes, L.; Caljon, G.; Delputte, P.; Cappoen, D.; Cos, P.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has developed a wide range of virulence factors to evade the immune system of which the polysaccharide capsule is the most important one. Formation of this capsule is dependent on the cps gene locus, but also involves other genes—like galU. The pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of prokaryotes and is required for the biosynthesis of capsular polysaccharides. In this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence using a Galleria mellonella model has been studied. We show that the mutation improves streptococcal adherence to epithelial cells and macrophage phagocytosis in vitro, while there is no definitive correlation on biofilm formation between parent and mutant strains. Moreover, in vivo virulence is attenuated for all mutated strains. Together, these results demonstrate that a galU mutation in S. pneumoniae influences host cell interactions in vitro and in vivo and can strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is worth investigating further as a potential drug target.
Fil: Cools, F.. Universiteit Antwerp; Bélgica
Fil: Torfs, E.. Universiteit Antwerp; Bélgica
Fil: Vanhoutte, B.. Universiteit Antwerp; Bélgica
Fil: Bidart De Macedo, M.. Universiteit Antwerp; Bélgica
Fil: Bonofiglio, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Mollerach, Marta Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Maes, L.. Universiteit Antwerp; Bélgica
Fil: Caljon, G.. Universiteit Antwerp; Bélgica
Fil: Delputte, P.. Universiteit Antwerp; Bélgica
Fil: Cappoen, D.. Universiteit Antwerp; Bélgica
Fil: Cos, P.. Universiteit Antwerp; Bélgica
Materia
BIOFILM
CELLULAR INTERACTIONS
GALLERIA MELLONELLA
GALU
STREPTOCOCCUS PNEUMONIAE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/100436
Acceder
id CONICETDig_980acc12c8202fe20cb969495aa820cd
oai_identifier_str oai:ri.conicet.gov.ar:11336/100436
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivoCools, F.Torfs, E.Vanhoutte, B.Bidart De Macedo, M.Bonofiglio, LauraMollerach, Marta EugeniaMaes, L.Caljon, G.Delputte, P.Cappoen, D.Cos, P.BIOFILMCELLULAR INTERACTIONSGALLERIA MELLONELLAGALUSTREPTOCOCCUS PNEUMONIAEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has developed a wide range of virulence factors to evade the immune system of which the polysaccharide capsule is the most important one. Formation of this capsule is dependent on the cps gene locus, but also involves other genes—like galU. The pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of prokaryotes and is required for the biosynthesis of capsular polysaccharides. In this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence using a Galleria mellonella model has been studied. We show that the mutation improves streptococcal adherence to epithelial cells and macrophage phagocytosis in vitro, while there is no definitive correlation on biofilm formation between parent and mutant strains. Moreover, in vivo virulence is attenuated for all mutated strains. Together, these results demonstrate that a galU mutation in S. pneumoniae influences host cell interactions in vitro and in vivo and can strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is worth investigating further as a potential drug target.Fil: Cools, F.. Universiteit Antwerp; BélgicaFil: Torfs, E.. Universiteit Antwerp; BélgicaFil: Vanhoutte, B.. Universiteit Antwerp; BélgicaFil: Bidart De Macedo, M.. Universiteit Antwerp; BélgicaFil: Bonofiglio, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Mollerach, Marta Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Maes, L.. Universiteit Antwerp; BélgicaFil: Caljon, G.. Universiteit Antwerp; BélgicaFil: Delputte, P.. Universiteit Antwerp; BélgicaFil: Cappoen, D.. Universiteit Antwerp; BélgicaFil: Cos, P.. Universiteit Antwerp; BélgicaOxford University Press2018-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100436Cools, F.; Torfs, E.; Vanhoutte, B.; Bidart De Macedo, M.; Bonofiglio, Laura; et al.; Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo; Oxford University Press; Pathogens and Disease; 76; 7; 10-2018; 1-102049-632XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/femspd/fty069info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/femspd/article/76/7/fty069/5078866info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:48:43Zoai:ri.conicet.gov.ar:11336/100436instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 10:48:43.899CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
title Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
spellingShingle Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
Cools, F.
BIOFILM
CELLULAR INTERACTIONS
GALLERIA MELLONELLA
GALU
STREPTOCOCCUS PNEUMONIAE
title_short Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
title_full Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
title_fullStr Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
title_full_unstemmed Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
title_sort Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo
dc.creator.none.fl_str_mv Cools, F.
Torfs, E.
Vanhoutte, B.
Bidart De Macedo, M.
Bonofiglio, Laura
Mollerach, Marta Eugenia
Maes, L.
Caljon, G.
Delputte, P.
Cappoen, D.
Cos, P.
author Cools, F.
author_facet Cools, F.
Torfs, E.
Vanhoutte, B.
Bidart De Macedo, M.
Bonofiglio, Laura
Mollerach, Marta Eugenia
Maes, L.
Caljon, G.
Delputte, P.
Cappoen, D.
Cos, P.
author_role author
author2 Torfs, E.
Vanhoutte, B.
Bidart De Macedo, M.
Bonofiglio, Laura
Mollerach, Marta Eugenia
Maes, L.
Caljon, G.
Delputte, P.
Cappoen, D.
Cos, P.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BIOFILM
CELLULAR INTERACTIONS
GALLERIA MELLONELLA
GALU
STREPTOCOCCUS PNEUMONIAE
topic BIOFILM
CELLULAR INTERACTIONS
GALLERIA MELLONELLA
GALU
STREPTOCOCCUS PNEUMONIAE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has developed a wide range of virulence factors to evade the immune system of which the polysaccharide capsule is the most important one. Formation of this capsule is dependent on the cps gene locus, but also involves other genes—like galU. The pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of prokaryotes and is required for the biosynthesis of capsular polysaccharides. In this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence using a Galleria mellonella model has been studied. We show that the mutation improves streptococcal adherence to epithelial cells and macrophage phagocytosis in vitro, while there is no definitive correlation on biofilm formation between parent and mutant strains. Moreover, in vivo virulence is attenuated for all mutated strains. Together, these results demonstrate that a galU mutation in S. pneumoniae influences host cell interactions in vitro and in vivo and can strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is worth investigating further as a potential drug target.
Fil: Cools, F.. Universiteit Antwerp; Bélgica
Fil: Torfs, E.. Universiteit Antwerp; Bélgica
Fil: Vanhoutte, B.. Universiteit Antwerp; Bélgica
Fil: Bidart De Macedo, M.. Universiteit Antwerp; Bélgica
Fil: Bonofiglio, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Mollerach, Marta Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina
Fil: Maes, L.. Universiteit Antwerp; Bélgica
Fil: Caljon, G.. Universiteit Antwerp; Bélgica
Fil: Delputte, P.. Universiteit Antwerp; Bélgica
Fil: Cappoen, D.. Universiteit Antwerp; Bélgica
Fil: Cos, P.. Universiteit Antwerp; Bélgica
description Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has developed a wide range of virulence factors to evade the immune system of which the polysaccharide capsule is the most important one. Formation of this capsule is dependent on the cps gene locus, but also involves other genes—like galU. The pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of prokaryotes and is required for the biosynthesis of capsular polysaccharides. In this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence using a Galleria mellonella model has been studied. We show that the mutation improves streptococcal adherence to epithelial cells and macrophage phagocytosis in vitro, while there is no definitive correlation on biofilm formation between parent and mutant strains. Moreover, in vivo virulence is attenuated for all mutated strains. Together, these results demonstrate that a galU mutation in S. pneumoniae influences host cell interactions in vitro and in vivo and can strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is worth investigating further as a potential drug target.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/100436
Cools, F.; Torfs, E.; Vanhoutte, B.; Bidart De Macedo, M.; Bonofiglio, Laura; et al.; Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo; Oxford University Press; Pathogens and Disease; 76; 7; 10-2018; 1-10
2049-632X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100436
identifier_str_mv Cools, F.; Torfs, E.; Vanhoutte, B.; Bidart De Macedo, M.; Bonofiglio, Laura; et al.; Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo; Oxford University Press; Pathogens and Disease; 76; 7; 10-2018; 1-10
2049-632X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/femspd/fty069
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/femspd/article/76/7/fty069/5078866
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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