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ResearchIn-Press PreviewInfectious diseaseMicrobiology Free access | 10.1172/JCI136737

CC17 Group B Streptococcus exploits integrins for neonatal meningitis development

Romain Deshayes de Cambronne,1 Agnès Fouet,2 Amandine Picart,1 Anne-Sophie Bourrel,1 Cyril Anjou,1 Guillaume Bouvier,3 Cristina Candeias,1 Abdelouhab Bouaboud,1 Lionel Costa,1 Anne-Cécile Boulay,4 Martine Cohen-Salmon,4 Isabelle Plu,5 Caroline Rambaud,6 Eva Faurobert,7 Corinne Albiges-Rizo,7 Asmaa Tazi,1 Claire Poyart,1 and Julie Guignot1

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

Find articles by Deshayes de Cambronne, R. in: JCI | PubMed | Google Scholar |

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

Find articles by Fouet, A. in: JCI | PubMed | Google Scholar |

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

Find articles by Bourrel, A. in: JCI | PubMed | Google Scholar

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

Find articles by Candeias, C. in: JCI | PubMed | Google Scholar

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

Find articles by Plu, I. in: JCI | PubMed | Google Scholar |

1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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1INSERM U1016, Institut Cochin, Université de Paris, Paris, France

2INSERMU1016, Institut Cochin, Université de Paris, Paris, France

3Structural Bioinformatics Unit, Department of Structural Biology and Chemis, Institut Pasteur, Paris, France

4Center for Interdisciplinary Research in Biology, Collège de France, Paris, France

5Département de neuropathologie, hopital de la pitié salpêtrière, Sorbonne Université, Paris, France

6Service d’anatomie-pathologique et médecine légale. Hôpital Raymond Poincar, Université Paris-Saclay, Garche, France

7Institute for Advanced Biosciences, University of Grenoble, Grenoble, France

8Institute for Advanced Biosciences, University of Grenoble, la tronche, France

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Published January 19, 2021 - More info

J Clin Invest. https://doi.org/10.1172/JCI136737.
Copyright © 2021, American Society for Clinical Investigation
Published January 19, 2021 - Version history
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Abstract

Group B Streptococcus (GBS) is the major cause of human neonatal infections. A single clone, designated CC17-GBS, accounts for more than 80% of meningitis cases, the most severe form of the infection. However, the events allowing blood-borne GBS to penetrate the brain remain largely elusive. In this study, we identified the host transmembrane receptors α5β1 and αvβ3 integrins as the ligands of Srr2, a major CC17-GBS specific adhesin. Two motifs located in the binding region of Srr2 were responsible for the interaction between CC17-GBS and these integrins. We demonstrated, in a blood-brain barrier cellular model, that both integrins contributed to the adhesion and internalization of CC17-GBS. Strikingly, both integrins were overexpressed during the post-natal period in the brain vessels of the blood-brain and blood-cerebrospinal fluid barriers and contributed to the juvenile susceptibility to CC17-meningitis. Finally, blocking these integrins decreased CC17-GBS crossing into the juvenile mice central nervous system in an in vivo model of meningitis.Our study demonstrates that CC17-GBS exploits integrins for crossing the brain vessels leading to meningitis. Importantly, it provides host molecular insights into neonate’s susceptibility to CC17-GBS meningitis, thereby opening new perspectives for therapeutic and prevention strategies of GBS-elicited meningitis.

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