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

Vinai Chittezham Thomas ¹, Marat R Sadykov ¹, Sujata S Chaudhari ¹

⁰Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.

Plos Pathogens +

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June 20, 2014

View abstract on PubMed

Summary

Bacterial biofilm development benefits from programmed cell death, controlled by metabolic pathways. CidC promotes cell death via acetate, while AlsSD counters it by diverting carbon flux, impacting biofilm and disease outcomes.

Area Of Science

Microbiology
Molecular Biology
Biochemistry

Background

Cell death is crucial for bacterial biofilm development, similar to eukaryotic processes.
Mechanisms controlling population-level cell death in bacteria remain poorly understood.

Purpose Of The Study

To investigate the role of metabolic overflow pathways in regulating cell death during staphylococcal biofilm development.
To elucidate the mechanisms by which CidC and AlsSD modulate cell death and biofilm biomass.
To explore the implications of metabolic control of cell death on disease outcomes.

Main Methods

Analysis of CidR-dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) pathways.
Metabolic flux analysis during staphylococcal biofilm formation.
Assessment of intracellular acidification, respiratory inhibition, and reactive oxygen species generation.
Evaluation of DNA damage and biofilm-dependent disease models.

Main Results

CidC activity generates acetate, inducing cell death through intracellular acidification and respiratory inhibition.
AlsSD activity counteracts CidC by diverting carbon flux to neutral byproducts and consuming protons.
Metabolically induced cell death shares features with eukaryotic programmed cell death, including ROS generation and DNA damage.
Metabolic modulation of cell death influences biofilm development and disease progression.

Conclusions

CidC and AlsSD metabolic pathways are key regulators of cell death in staphylococcal biofilms.
Metabolic control of cell death impacts both biofilm structure and virulence.
The metabolic regulation of cell death may be a fundamental prokaryotic developmental strategy.

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