Journal Article

CC17 group B Streptococcus exploits integrins for neonatal meningitis development

Fouet, Agnes, Costa, Lionel, Poyart, Claire, de Cambronne, Romain Deshayes, Tazi, Asmaa, Boulay, Anne-Cécile, Faurobert, Eva, Bouaboud, Abdelouhab, Plu, Isabelle, Albiges-Rizo, Corinne, Candeias, Cristina, Rambaud, Caroline, Bourrel, Anne-Sophie, Cohen-Salmon, Martine, Bouvier, Guillaume, Anjou, Cyril, Picart, Amandine, Guignot, Julie

2021

Overview

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 a5β1 and avß3 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 CC17GBS 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.

• Publisher: American Society for Clinical Investigation
• Subject: Binding sites / Biomedical research / Blood-brain barrier / Cerebrospinal fluid / Infections / Integrins / Internalization / Ligands / Meningitis / Neonates / Newborn babies / Pathogens / Peptides / Proteins / Streptococcus / Streptococcus infections