WhyD tailors surface polymers to prevent premature bacteriolysis and direct cell elongation in Streptococcus pneumoniae

  1. Josué Flores-Kim
  2. Genevieve S Dobihal
  3. Thomas G Bernhardt
  4. David Z Rudner  Is a corresponding author
  1. Harvard Medical School, United States
  2. Howard Hughes Medical Institute, Harvard Medical School, United States

Abstract

Penicillin and related antibiotics disrupt cell wall synthesis in bacteria causing the downstream misactivation of cell wall hydrolases called autolysins to induce cell lysis. Despite the clinical importance of this phenomenon, little is known about the factors that control autolysins and how penicillins subvert this regulation to kill cells. In the pathogen Streptococcus pneumoniae (Sp), LytA is the major autolysin responsible for penicillin-induced bacteriolysis. We recently discovered that penicillin treatment of Sp causes a dramatic shift in surface polymer biogenesis in which cell wall-anchored teichoic acids (WTAs) increase in abundance at the expense of lipid-linked teichoic acids (LTAs). Because LytA binds to both species of teichoic acids, this change recruits the enzyme to its substrate where it cleaves the cell wall and elicits lysis. In this report, we identify WhyD (SPD_0880) as a new factor that controls the level of WTAs in Sp cells to prevent LytA misactivation during exponential growth and premature lysis. We show that WhyD is a WTA hydrolase that restricts the WTA content of the wall to areas adjacent to active PG synthesis. Our results support a model in which the WTA tailoring activity of WhyD during exponential growth directs PG remodeling activity required for proper cell elongation in addition to preventing autolysis by LytA.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all Figures.

Article and author information

Author details

  1. Josué Flores-Kim

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8282-6647
  2. Genevieve S Dobihal

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7589-1133
  3. Thomas G Bernhardt

    Department of Microbiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3566-7756
  4. David Z Rudner

    Department of Microbiology, Harvard Medical School, Boston, United States
    For correspondence
    rudner@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0236-7143

Funding

National Institute of Allergy and Infectious Diseases (F32AI36431)

  • Josué Flores-Kim

National Institute of Allergy and Infectious Diseases (R01AI083365)

  • Thomas G Bernhardt

Howard Hughes Medical Institute

  • Thomas G Bernhardt

National Institute of General Medical Sciences (R01GM127399)

  • David Z Rudner

National Institute of General Medical Sciences (R01GM086466)

  • David Z Rudner

National Institute of Allergy and Infectious Diseases (R01AI139083)

  • Thomas G Bernhardt
  • David Z Rudner

National Institute of Allergy and Infectious Diseases (T32AI132120)

  • Genevieve S Dobihal

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

Reviewing Editor

  1. Tâm Mignot, CNRS-Aix Marseille University, France

Version history

  1. Received: December 15, 2021
  2. Preprint posted: January 9, 2022 (view preprint)
  3. Accepted: May 19, 2022
  4. Accepted Manuscript published: May 20, 2022 (version 1)
  5. Accepted Manuscript updated: May 24, 2022 (version 2)
  6. Version of Record published: June 20, 2022 (version 3)

Copyright

© 2022, Flores-Kim 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.

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  1. Josué Flores-Kim
  2. Genevieve S Dobihal
  3. Thomas G Bernhardt
  4. David Z Rudner
(2022)
WhyD tailors surface polymers to prevent premature bacteriolysis and direct cell elongation in Streptococcus pneumoniae
eLife 11:e76392.
https://doi.org/10.7554/eLife.76392

Share this article

https://doi.org/10.7554/eLife.76392

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