1. Microbiology and Infectious Disease
Download icon

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

Research Article
  • Cited 1
  • Views 587
  • Annotations
Cite this article as: eLife 2019;8:e48772 doi: 10.7554/eLife.48772

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.

Article and author information

Author details

  1. Constantin Hays

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Gérald Touak

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Abdelouhab Bouaboud

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Agnès Fouet

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Julie Guignot

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Claire Poyart

    Team Bacteria and Perinatality, Institut Cochin, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. 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.
    ORCID icon "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.

Reviewing Editor

  1. Sophie Helaine, Imperial College London, United Kingdom

Publication history

  1. Received: May 24, 2019
  2. Accepted: November 9, 2019
  3. Accepted Manuscript published: November 11, 2019 (version 1)
  4. Version of Record published: November 20, 2019 (version 2)

Copyright

© 2019, Hays et al.

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.

Metrics

  • 587
    Page views
  • 101
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Microbiology and Infectious Disease
    Pradyot Bhattacharya et al.
    Research Article Updated

    HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease
    Jeannette L Tenthorey et al.
    Research Article

    Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase weak antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.