A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection

Detalhes bibliográficos
Autor(a) principal: Andrade, Elva Bonifácio
Data de Publicação: 2018
Outros Autores: Magalhães, Ana, Puga, Ana, Costa, Madalena, Bravo, Joana, Portugal, Camila Cabral, Ribeiro, Adília, Correia-Neves, M, Faustino, Augusto, Firon, Arnaud, Trieu-Cuot, Patrick, Summavielle, Teresa, Ferreira, Paula
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/57779
Resumo: Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.
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spelling A mouse model reproducing the pathophysiology of neonatal group B streptococcal infectionAnimalsAnimals, NewbornBehavior, AnimalBody WeightFemaleHemolysin ProteinsInflammationMaleMaze LearningMeningitisMeningitis, BacterialMiceMice, Inbred BALB CPerforinPregnancyPregnancy, AnimalStreptococcal InfectionsStreptococcus agalactiaeVaginaDisease Models, AnimalInfectious Disease Transmission, VerticalScience & TechnologyGroup B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.The authors gratefully acknowledge the help of Encarnaca̧ ̃o Ribeiro for excellent technical assistance, Joana Tavares for assisting with IVIS Lumina LT, Susana Roque for the luminex instrument experiments, the Molecular Microbiology group at i3S for microscope use, and the Portuguese architect and artist Gil Ferreira da Silva for the artworks included in the last figure. This work was supported by funds from Foundation for Science and Technology (FCT), European Regional Development Fund (FEDER) and Compete under project POCI-01-0145-FEDER-016607 (PTDC/IMI-MIC/1049/2014) and from the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). T.S. and A.M. were supported by Investigador FCT (IF/00875/2012 and IF/00753/2014), POPH and Fundo Social Europeu. E.B.A. and C.C.P. hold postdoctoral fellowships from FCT (PTDC/IMI-MIC/1049/2014 and SFRH/BPD/91962/2012). Ar.F. and P.T.C. were supported by Laboratoire d’Excellence (LABEX) Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID).info:eu-repo/semantics/publishedVersionNature Publishing Group (NPG)Universidade do MinhoAndrade, Elva BonifácioMagalhães, AnaPuga, AnaCosta, MadalenaBravo, JoanaPortugal, Camila CabralRibeiro, AdíliaCorreia-Neves, MFaustino, AugustoFiron, ArnaudTrieu-Cuot, PatrickSummavielle, TeresaFerreira, Paula20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/57779eng2041-172310.1038/s41467-018-05492-y30087335info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:37:48Zoai:repositorium.sdum.uminho.pt:1822/57779Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:34:08.701892Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
title A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
spellingShingle A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
Andrade, Elva Bonifácio
Animals
Animals, Newborn
Behavior, Animal
Body Weight
Female
Hemolysin Proteins
Inflammation
Male
Maze Learning
Meningitis
Meningitis, Bacterial
Mice
Mice, Inbred BALB C
Perforin
Pregnancy
Pregnancy, Animal
Streptococcal Infections
Streptococcus agalactiae
Vagina
Disease Models, Animal
Infectious Disease Transmission, Vertical
Science & Technology
title_short A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
title_full A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
title_fullStr A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
title_full_unstemmed A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
title_sort A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
author Andrade, Elva Bonifácio
author_facet Andrade, Elva Bonifácio
Magalhães, Ana
Puga, Ana
Costa, Madalena
Bravo, Joana
Portugal, Camila Cabral
Ribeiro, Adília
Correia-Neves, M
Faustino, Augusto
Firon, Arnaud
Trieu-Cuot, Patrick
Summavielle, Teresa
Ferreira, Paula
author_role author
author2 Magalhães, Ana
Puga, Ana
Costa, Madalena
Bravo, Joana
Portugal, Camila Cabral
Ribeiro, Adília
Correia-Neves, M
Faustino, Augusto
Firon, Arnaud
Trieu-Cuot, Patrick
Summavielle, Teresa
Ferreira, Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Andrade, Elva Bonifácio
Magalhães, Ana
Puga, Ana
Costa, Madalena
Bravo, Joana
Portugal, Camila Cabral
Ribeiro, Adília
Correia-Neves, M
Faustino, Augusto
Firon, Arnaud
Trieu-Cuot, Patrick
Summavielle, Teresa
Ferreira, Paula
dc.subject.por.fl_str_mv Animals
Animals, Newborn
Behavior, Animal
Body Weight
Female
Hemolysin Proteins
Inflammation
Male
Maze Learning
Meningitis
Meningitis, Bacterial
Mice
Mice, Inbred BALB C
Perforin
Pregnancy
Pregnancy, Animal
Streptococcal Infections
Streptococcus agalactiae
Vagina
Disease Models, Animal
Infectious Disease Transmission, Vertical
Science & Technology
topic Animals
Animals, Newborn
Behavior, Animal
Body Weight
Female
Hemolysin Proteins
Inflammation
Male
Maze Learning
Meningitis
Meningitis, Bacterial
Mice
Mice, Inbred BALB C
Perforin
Pregnancy
Pregnancy, Animal
Streptococcal Infections
Streptococcus agalactiae
Vagina
Disease Models, Animal
Infectious Disease Transmission, Vertical
Science & Technology
description Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/57779
url http://hdl.handle.net/1822/57779
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2041-1723
10.1038/s41467-018-05492-y
30087335
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group (NPG)
publisher.none.fl_str_mv Nature Publishing Group (NPG)
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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