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Nature CommunicationsVolume 9, Issue 1, 1 December 2018, Article number 3138

A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection(Article)(Open Access)

  • Andrade, E.B.,
  • Magalhães, A.,
  • Puga, A.,
  • Costa, M.,
  • Bravo, J.,
  • Portugal, C.C.,
  • Ribeiro, A.,
  • Correia-Neves, M.,
  • Faustino, A.,
  • Firon, A.,
  • Trieu-Cuot, P.,
  • Summavielle, T.,
  • Ferreira, P.
  • View Correspondence (jump link)
  • aICBAS—Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, 4150-313, Portugal
  • bi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal
  • cIBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4200-135, Portugal
  • dESS—Escola Superior de Saúde, Instituto Politécnico do Porto, Porto, 4200-072, Portugal
  • eUMIB—Unit for Multidisciplinary Investigation in Biomedicine (Endocrine, Cardiovascular & Metabolic Research), University of Porto, Porto, 4150-313, Portugal
  • fLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, 4710-057, Portugal
  • gICVS/3B’s, PT Government Associate Laboratory, 4710-057 Braga/4805-017, Guimarães, Portugal
  • hDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, 171 76, Stockholm, Sweden
  • iInstitut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-positif, Centre National de la Recherche Scientifique (CNRS ERL 6002), Paris, 75015, France

Abstract

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. © 2018, The Author(s).

Indexed keywords

EMTREE drug terms:aspartate aminotransferasecreatine kinasecreatininecytolysinhemolysinnitrogenureaperforin
GEOBASE Subject Index:bacterial diseasedevelopmental biologyinfectious diseasemeningitismortalitymutationneonatenumerical modelparasite transmissionphysiology
EMTREE medical terms:adultanimal cellanimal experimentanimal modelanimal tissueArticleaspartate aminotransferase blood levelbacterial colonizationbacterial strainbacterial transmissionbacterial virulencecontrolled studycreatine kinase blood levelcreatinine blood leveldevelopmental disorderembryoexperimental pneumoniafemalegroup B streptococcal pneumoniagroup b streptococcal strain bm110learning disordermemory disordermortality ratemousemutantnewbornnonhumanprogenyStreptococcus agalactiaeurea nitrogen blood levelvertical transmissionanimalanimal behaviorbacterial meningitisBagg albino mousebody weightbreedingchemistrydisease modelinflammationmalemaze testmeningitismicrobiologypathogenicitypathophysiologypregnancyStreptococcus infectiontransmissionvaginavertical transmission
Species Index:Animalia
MeSH:AnimalsAnimals, NewbornBehavior, AnimalBody WeightDisease Models, AnimalFemaleHemolysin ProteinsInfectious Disease Transmission, VerticalInflammationMaleMaze LearningMeningitisMeningitis, BacterialMiceMice, Inbred BALB CPerforinPregnancyPregnancy, AnimalStreptococcal InfectionsStreptococcus agalactiaeVagina

Chemicals and CAS Registry Numbers:

aspartate aminotransferase, 9000-97-9; creatine kinase, 9001-15-4; creatinine, 19230-81-0, 60-27-5; nitrogen, 7727-37-9; urea, 57-13-6; perforin, 119332-27-3;

Hemolysin Proteins; Perforin

Funding details

Funding sponsor Funding number Acronym
Fundação Portugal TelecomIF/00753/2014,IF/00875/2012
LABEX
Fundação para a Ciência e a Tecnologia
See opportunities
ANR-10-LABX-62-IBEID
Fundação para a Ciência e a Tecnologia
See opportunities
European Regional Development FundPOCI-01-0145-FEDER-016607,NORTE-01-0145-FEDER-000012,PTDC/IMI-MIC/1049/2014
NORTE 2020

  • 1

    The authors gratefully acknowledge the help of Encarnaca̧ ̃ 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).

  • ISSN: 20411723
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1038/s41467-018-05492-y
  • PubMed ID: 30087335
  • Document Type: Article
  • Publisher: Nature Publishing Group

  Ferreira, P.; ICBAS—Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal;
© Copyright 2018 Elsevier B.V., All rights reserved.

Cited by 6 documents

Allard, M.-J. , Giraud, A. , Segura, M.
Sex-specific maternofetal innate immune responses triggered by group B Streptococci
(2019) Scientific Reports
Botelho, R.M. , Tenorio, L.P.G. , Silva, A.L.M.
Biomechanical and functional properties of trophoblast cells exposed to Group B Streptococcus in vitro and the beneficial effects of uvaol treatment
(2019) Biochimica et Biophysica Acta - General Subjects
Gres, V. , Kolter, J. , Erny, D.
The role of CNS macrophages in streptococcal meningoencephalitis
(2019) Journal of Leukocyte Biology
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