A Central Role for Carbon-Overflow Pathways in the Modulation of Bacterial Cell Death

PLoS Pathogens

Matthew C. Zimmerman¹  Joselyn Jones¹  Sujata S. Chaudhari²  Todd J. Widhelm²  Kenneth W. Bayles²  Marat R. Sadykov²  Vinai Chittezham Thomas²  Jong-Sam Ahn²  Jennifer L. Endres²  Randeep S. Jawa³ 

[1] Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America;Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America;Department of Surgery, Stony Brook University School of Medicine, Stony Brook, New York, United States of America

关键词: Cell death;    Staphylococcus aureus;    Glucose;    Bacterial biofilms;    Glucose metabolism;    Pyruvate;    Apoptosis;    Biofilms;   

DOI  :  10.1371/journal.ppat.1004205

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY