WhyD tailors surface polymers to prevent premature bacteriolysis and direct cell elongation in Streptococcus pneumoniae
- Harvard Medical School, United States
- 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
Genevieve S Dobihal
Thomas G Bernhardt
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.
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.
Metrics
-
- 1,493
- views
-
- 298
- downloads
-
- 6
- 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)
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
Further reading
-
- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
In the bacterium M. smegmatis, an enzyme called MftG allows the cofactor mycofactocin to transfer electrons released during ethanol metabolism to the electron transport chain.
-
- Microbiology and Infectious Disease
Bacterial regional demonstration after global dissemination is an essential pathway for selecting distinct finesses. However, the evolution of the resistome during the transition to endemicity remains unaddressed. Using the most comprehensive whole-genome sequencing dataset of Salmonella enterica serovar Gallinarum (S. Gallinarum) collected from 15 countries, including 45 newly recovered samples from two related local regions, we established the relationship among avian-specific pathogen genetic profiles and localization patterns. Initially, we revealed the international transmission and evolutionary history of S. Gallinarum to recent endemicity through phylogenetic analysis conducted using a spatiotemporal Bayesian framework. Our findings indicate that the independent acquisition of the resistome via the mobilome, primarily through plasmids and transposons, shapes a unique antimicrobial resistance profile among different lineages. Notably, the mobilome-resistome combination among distinct lineages exhibits a geographical-specific manner, further supporting a localized endemic mobilome-driven process. Collectively, this study elucidates resistome adaptation in the endemic transition of an avian-specific pathogen, likely driven by the localized farming style, and provides valuable insights for targeted interventions.
