CC17 group B Streptococcus exploits integrins for neonatal meningitis development

J Clin Invest. 2021 Mar 1;131(5):e136737. doi: 10.1172/JCI136737.


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.

Keywords: Bacterial infections; Infectious disease; Integrins; Microbiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Animals
  • Animals, Newborn
  • Bacterial Adhesion / genetics
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / microbiology
  • Cell Line
  • Humans
  • Integrin alphaVbeta3 / genetics
  • Integrin alphaVbeta3 / metabolism*
  • Meningitis, Bacterial / genetics
  • Meningitis, Bacterial / metabolism*
  • Rats
  • Receptors, Vitronectin / genetics
  • Receptors, Vitronectin / metabolism*
  • Streptococcal Infections / genetics
  • Streptococcal Infections / metabolism*
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / metabolism*


  • Adhesins, Bacterial
  • Integrin alphaVbeta3
  • Receptors, Vitronectin
  • integrin alphavbeta1