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- Title
CC17 group B Streptococcus exploits integrins for neonatal meningitis development.
- Authors
Deshayes de Cambronne, Romain; Fouet, Agnès; Picart, Amandine; Bourrel, Anne-Sophie; Anjou, Cyril; Bouvier, Guillaume; Candeias, Cristina; Bouaboud, Abdelouhab; Costa, Lionel; Boulay, Anne-Cécile; Cohen-Salmon, Martine; Plu, Isabelle; Rambaud, Caroline; Faurobert, Eva; Albiges-Rizo, Corinne; Tazi, Asmaa; Poyart, Claire; Guignot, Julie; Albigès-Rizo, Corinne
- 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.
- Subjects
STREPTOCOCCUS agalactiae; INTEGRINS; BLOOD-brain barrier; MENINGITIS; NEONATAL infections
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 5, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI136737