A central role for carbon-overflow pathways in the modulation of bacterial cell death.

Authors

Vinai Chittezham Thomas, University of Nebraska Medical CenterFollow
Marat Sadykov, University of Nebraska Medical CenterFollow
Sujata S. Chaudhari, University of Nebraska Medical CenterFollow
Joselyn Jones, University of Nebraska Medical Center
Jennifer L. Endres, University of Nebraska Medical CenterFollow
Todd J. Widhelm, University of Nebraska Medical Center
Jong-Sam Ahn, University of Nebraska Medical CenterFollow
Randeep S. Jawa, Stony Brook University School of Medicine
Matthew C. Zimmerman, University of Nebraska Medical CenterFollow
Kenneth W. Bayles, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

PLoS Pathogens

Publication Date

Summer 6-19-2014

Volume

10

Abstract

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux towards neutral rather than acidic byproducts and consuming intracellular protons in the process. Furthermore, the physiological features that accompany metabolic activation of cell death bears remarkable similarities to hallmarks of eukaryotic programmed cell death, including the generation of reactive oxygen species and DNA damage. Finally, we demonstrate that the metabolic modulation of cell death not only affects biofilm development but also biofilm-dependent disease outcomes. Given the ubiquity of such carbon overflow pathways in diverse bacterial species, we propose that the metabolic control of cell death may be a fundamental feature of prokaryotic development.

MeSH Headings

Acetates, Acetolactate Synthase, Animals, Biofilms, Carbon, Carboxy-Lyases, DNA Damage, Endocarditis, Bacterial, Gene Expression Regulation, Bacterial, Oxygen Consumption, Pyruvate Oxidase, Rabbits, Reactive Oxygen Species, Staphylococcus aureus

DOI Link

10.1371/journal.ppat.1004205

ISSN

1553-7374

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Chittezham Thomas, Vinai; Sadykov, Marat; Chaudhari, Sujata S.; Jones, Joselyn; Endres, Jennifer L.; Widhelm, Todd J.; Ahn, Jong-Sam; Jawa, Randeep S.; Zimmerman, Matthew C.; and Bayles, Kenneth W., "A central role for carbon-overflow pathways in the modulation of bacterial cell death." (2014). Journal Articles: Pathology and Microbiology. 20.
https://digitalcommons.unmc.edu/com_pathmicro_articles/20