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CC17 group B Streptococcus exploits integrins for neonatal meningitis development
Romain Deshayes de Cambronne, … , Claire Poyart, Julie Guignot
Romain Deshayes de Cambronne, … , Claire Poyart, Julie Guignot
Published January 19, 2021
Citation Information: J Clin Invest. 2021;131(5):e136737. https://doi.org/10.1172/JCI136737.
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Research Article Infectious disease Microbiology Article has an altmetric score of 18

CC17 group B Streptococcus exploits integrins for neonatal meningitis development

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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.

Authors

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

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Figure 1

BRSrr2 recognizes α5β1 and αvβ3 integrins in a direct manner.

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BRSrr2 recognizes α5β1 and αvβ3 integrins in a direct manner.
(A) Schema...
(A) Schematic representation of Srr2 and Srr1 proteins with signal sequence (checkered), serine-rich regions (white), LP × TG cell wall anchoring motif (hatched), and the binding regions of Srr2 (black) or Srr1 (gray) delineated by dashed lines. Numbers in black indicate the position of amino acid residues, and letters in white indicate the predicted motifs of interaction with integrins. (B) Dot blotting was performed to determine the interaction between immobilized human α5β1 and αvβ3 integrins or ICAM1 and BRSrr2 or BRSrr1. Purified BRSrr2 and BRSrr1 proteins are shown in Supplemental Figure 1A. (C–E) Interaction of BRSrr2 (black squares) or BRSrr1 (gray circles) with human α5β1 integrin (C), αvβ3 integrin (D), or ICAM1 (E) were assessed by ELISA. Results were normalized to negative control (BSA). Statistical analysis: data shown are mean ± SEM of at least 3 independent experiments. Two-way ANOVA with Bonferroni’s multiple-comparison posttest was performed. NS, nonsignificant; *P < 0.05; **P < 0.01; ***P < 0.001.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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