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Updated: Nov 20, 2025
Induction of Leptomeningeal Cells Modification Via Intracisternal Injection
Published on: May 7, 2020
CC17 group B Streptococcus exploits integrins for neonatal meningitis development
Romain Deshayes de Cambronne1, Agnès Fouet1, Amandine Picart1
1Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.
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 postnatal period in the brain vessels of the blood-brain barrier and blood-cerebrospinal fluid barrier and contributed to juvenile susceptibility to CC17 meningitis. Finally, blocking these integrins decreased the ability of CC17-GBS to cross into the CNS of juvenile mice in an in vivo model of meningitis. Our study demonstrated that CC17-GBS exploits integrins in order to cross 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.
Insights
Group B Streptococcus (GBS) meningitis in newborns is often caused by CC17-GBS. This study reveals CC17-GBS uses host integrins to invade the brain, offering new therapeutic targets.
Area of Science:
- Microbiology
- Neuroscience
- Immunology
Background:
- Group B Streptococcus (GBS) is a leading cause of neonatal infections, with CC17-GBS responsible for most meningitis cases.
- The mechanism by which GBS crosses the blood-brain barrier to cause meningitis is not fully understood.
Purpose of the Study:
- To identify the molecular mechanisms by which CC17-GBS invades the central nervous system (CNS).
- To investigate the role of host integrins in CC17-GBS meningitis and neonate susceptibility.
Main Methods:
- Identified host integrin ligands for the CC17-GBS adhesin Srr2 using molecular interaction studies.
- Utilized a blood-brain barrier cellular model to assess GBS adhesion and internalization.
- Examined integrin expression in neonatal brain vasculature.
- Tested the efficacy of integrin blocking in a mouse model of neonatal meningitis.
Main Results:
- The CC17-GBS adhesin Srr2 binds to host integrins α5β1 and αvβ3 via specific motifs.
- These integrins mediate GBS adhesion and internalization across the blood-brain barrier model.
- Integrins α5β1 and αvβ3 are overexpressed in neonatal brain vessels and contribute to meningitis susceptibility.
- Blocking these integrins reduced GBS CNS invasion in juvenile mice.
Conclusions:
- CC17-GBS utilizes host integrins α5β1 and αvβ3 to facilitate CNS invasion and cause meningitis.
- Integrin overexpression during the neonatal period contributes to susceptibility to GBS meningitis.
- Targeting these integrins presents a potential therapeutic strategy for GBS meningitis.
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