A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , |
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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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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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