The alternative sigma factor σX mediates competence shut-off at the cell pole in Streptococcus pneumoniae

  1. Calum HG Johnston
  2. Anne-Lise Soulet
  3. Matthieu Bergé
  4. Marc Prudhomme
  5. David De Lemos
  6. Patrice Polard  Is a corresponding author
  1. CNRS, France
  2. University of Geneva, Switzerland
  3. Université Paul Sabatier, France

Abstract

Competence is a widespread bacterial differentiation program driving antibiotic resistance and virulence in many pathogens. Here, we studied the spatiotemporal localization dynamics of the key regulators that master the two intertwined and transient transcription waves defining competence in Streptococcus pneumoniae. The first wave relies on the stress-inducible phosphorelay between ComD and ComE proteins, and the second on the alternative sigma factor σX, which directs the expression of the DprA protein that turns off competence through interaction with phosphorylated ComE. We found that ComD, σX and DprA stably co-localize at one pole in competent cells, with σX physically conveying DprA next to ComD. Through this polar DprA targeting function, σX mediates the timely shut-off of the pneumococcal competence cycle, preserving cell fitness. Altogether, this study unveils an unprecedented role for a transcription σ factor in spatially coordinating the negative feedback loop of its own genetic circuit.

Data availability

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

Article and author information

Author details

  1. Calum HG Johnston

    LMGM-UMR5100, CNRS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Anne-Lise Soulet

    LMGM-UMR5100, CNRS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthieu Bergé

    Department Microbiology and Molecular Medicine, Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0910-6114
  4. Marc Prudhomme

    LMGM-UMR5100, Université Paul Sabatier, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  5. David De Lemos

    LMGM-UMR5100, CNRS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Patrice Polard

    LMGM-UMR5100, CNRS, Toulouse, France
    For correspondence
    Patrice.Polard@ibcg.biotoul.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0365-4347

Funding

Agence Nationale de la Recherche (ANR-10-BLAN-1331)

  • Patrice Polard

Agence Nationale de la Recherche (ANR-13-BSV8-0022)

  • Patrice Polard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Melanie Blokesch, Ecole Polytechnique Fédérale de Lausanne, Switzerland

Version history

  1. Received: September 8, 2020
  2. Accepted: October 31, 2020
  3. Accepted Manuscript published: November 2, 2020 (version 1)
  4. Version of Record published: November 13, 2020 (version 2)

Copyright

© 2020, Johnston 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

  • 1,061
    views
  • 141
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Calum HG Johnston
  2. Anne-Lise Soulet
  3. Matthieu Bergé
  4. Marc Prudhomme
  5. David De Lemos
  6. Patrice Polard
(2020)
The alternative sigma factor σX mediates competence shut-off at the cell pole in Streptococcus pneumoniae
eLife 9:e62907.
https://doi.org/10.7554/eLife.62907

Share this article

https://doi.org/10.7554/eLife.62907

Further reading

    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease
    Timothy A Bates, Mila Trank-Greene ... Fikadu G Tafesse
    Research Article

    Mycobacterium tuberculosis (Mtb) is known to survive within macrophages by compromising the integrity of the phagosomal compartment in which it resides. This activity primarily relies on the ESX-1 secretion system, predominantly involving the protein duo ESAT-6 and CFP-10. CFP-10 likely acts as a chaperone, while ESAT-6 likely disrupts phagosomal membrane stability via a largely unknown mechanism. we employ a series of biochemical analyses, protein modeling techniques, and a novel ESAT-6-specific nanobody to gain insight into the ESAT-6’s mode of action. First, we measure the binding kinetics of the tight 1:1 complex formed by ESAT-6 and CFP-10 at neutral pH. Subsequently, we demonstrate a rapid self-association of ESAT-6 into large complexes under acidic conditions, leading to the identification of a stable tetrameric ESAT-6 species. Using molecular dynamics simulations, we pinpoint the most probable interaction interface. Furthermore, we show that cytoplasmic expression of an anti-ESAT-6 nanobody blocks Mtb replication, thereby underlining the pivotal role of ESAT-6 in intracellular survival. Together, these data suggest that ESAT-6 acts by a pH-dependent mechanism to establish two-way communication between the cytoplasm and the Mtb-containing phagosome.

    1. Microbiology and Infectious Disease
    João Paulo Portela Catani, Anouk Smet ... Thorsten U Vogel
    Research Article

    Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses. However, antibodies directed against influenza neuraminidase (NA) also contribute to protection. Here, we analysed the antigenic diversity of a panel of N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. The antigenic breadth of these NAs was determined based on the NA inhibition (NAI) of a broad panel of ferret and mouse immune sera that were raised by infection and recombinant N2 NA immunisation. This assessment allowed us to distinguish at least four antigenic groups in the N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. Computational analysis further revealed that the amino acid residues in N2 NA that have a major impact on susceptibility to NAI by immune sera are in proximity of the catalytic site. Finally, a machine learning method was developed that allowed to accurately predict the impact of mutations that are present in our N2 NA panel on NAI. These findings have important implications for the renewed interest to develop improved influenza vaccines based on the inclusion of a protective NA antigen formulation.