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

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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.

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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

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Josué Flores-Kim

Department of Microbiology, Harvard Medical School, Boston, United States

For correspondence
Josue_FloresKim@hms.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8282-6647
Genevieve S Dobihal

Department of Microbiology, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7589-1133
Thomas G Bernhardt

Department of Microbiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States

For correspondence
thomas_bernhardt@hms.harvard.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3566-7756
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.

"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.

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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.