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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

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.

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