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ResearchIn-Press PreviewInfectious diseaseMicrobiology Free access | 10.1172/JCI136737
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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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
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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
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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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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
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.