Perinatal hormones favor CC17 Group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates

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Abstract

Group B Streptococcus (GBS) is the leading cause of invasive bacterial neonatal infections. Late-onset diseases (LOD) occur between 7 and 89 days of life and are largely due to the CC17 GBS hypervirulent clone. We studied the impact of estradiol (E2) and progesterone (P4), which impregnate the fetus during pregnancy, on GBS neonatal infection in cellular and mouse models of hormonal exposure corresponding to concentrations found at birth (E2-P4 C₀) and over 7 days old (E2-P4 C₇). Using representative GBS isolates, we show that E2-P4 C₇ concentrations specifically favor CC17 GBS meningitis following mice oral infection. CC17 GBS crosses the intestinal barrier through M cells. This process mediated by the CC17-specific surface protein Srr2 is enhanced by E2-P4 C₇ concentrations which promote M cell differentiation and CC17 GBS invasiveness. Our findings provide an explanation for CC17 GBS responsibility in LOD in link with neonatal gastrointestinal tract maturation and hormonal imprint.

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All data generated or analysed during this study are included in the manuscript.

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Constantin Hays

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Gérald Touak

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Abdelouhab Bouaboud

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Agnès Fouet

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Julie Guignot

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Claire Poyart

Team Bacteria and Perinatality, Institut Cochin, Paris, France

Competing interests
The authors declare that no competing interests exist.
Asmaa Tazi

Team Bacteria and Perinatality, Institut Cochin, Paris, France

For correspondence
asmaa.tazi@aphp.fr

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9531-9177

Funding

Fondation pour la Recherche Médicale (DBF20160635740)

Constantin Hays
Gérald Touak
Claire Poyart
Asmaa Tazi

This work was supported by the FRM, grant DBF20160635740. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethics

Animal experimentation: Work on animals was performed in compliance with French and European regulations on care and protection of laboratory animals (EC Directive 2010/63, French Law 2013-118, February 6, 2013). All experiments were approved by the Ethics Committee of the Paris Descartes University (Permit numbers APAFIS#390 and APAFIS#17106). Animals were not involved in any previous procedure.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.