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

被引:89
作者
Thomas, Vinai Chittezham [1 ]
Sadykov, Marat R. [1 ]
Chaudhari, Sujata S. [1 ]
Jones, Joselyn [2 ]
Endres, Jennifer L. [1 ]
Widhelm, Todd J. [1 ]
Ahn, Jong-Sam [1 ]
Jawa, Randeep S. [3 ]
Zimmerman, Matthew C. [2 ]
Bayles, Kenneth W. [1 ]
机构
[1] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Ctr Staphylococcal Res, Omaha, NE 68198 USA
[2] Univ Nebraska Med Ctr, Omaha, NE USA
[3] SUNY Stony Brook, Sch Med, Dept Surg, Stony Brook, NY 11794 USA
关键词
STAPHYLOCOCCUS-AUREUS; PYRUVATE OXIDASE; LACTOBACILLUS-PLANTARUM; ENTEROCOCCUS-FAECALIS; BACILLUS-SUBTILIS; INDUCED APOPTOSIS; GENE ENCODES; ACID STRESS; METABOLISM; LYSIS;
D O I
10.1371/journal.ppat.1004205
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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 a-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.
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页数:13
相关论文
共 47 条
[1]   The Tangled Circuitry of Metabolism and Apoptosis [J].
Andersen, Joshua L. ;
Kornbluth, Sally .
MOLECULAR CELL, 2013, 49 (03) :399-410
[2]   The biological role of death and lysis in biofilm development [J].
Bayles, Kenneth W. .
NATURE REVIEWS MICROBIOLOGY, 2007, 5 (09) :721-726
[3]  
Booth I.R., 2003, Food Preservatives, P25
[4]   BapE DNA endonuclease induces an apoptotic-like response to DNA damage in Caulobacter [J].
Bos, Julia ;
Yakhnina, Anastasiya A. ;
Gitai, Zemer .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (44) :18096-18101
[5]   Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus [J].
Dhawan, VK ;
Yeaman, MR ;
Cheung, AL ;
Kim, E ;
Sullam, PM ;
Bayer, AS .
INFECTION AND IMMUNITY, 1997, 65 (08) :3293-3299
[6]   Antibiotic-Induced Bacterial Cell Death Exhibits Physiological and Biochemical Hallmarks of Apoptosis [J].
Dwyer, Daniel J. ;
Camacho, Diogo M. ;
Kohanski, Michael A. ;
Callura, Jarred M. ;
Collins, James J. .
MOLECULAR CELL, 2012, 46 (05) :561-572
[7]   Two Programmed Cell Death Systems in Escherichia coli: An Apoptotic-Like Death Is Inhibited by the mazEF-Mediated Death Pathway [J].
Erental, Ariel ;
Sharon, Idith ;
Engelberg-Kulka, Hanna .
PLOS BIOLOGY, 2012, 10 (03)
[8]  
Furlong IJ, 1997, J CELL SCI, V110, P653
[9]   Sugar-induced apoptosis in yeast cells [J].
Granot, D ;
Levine, A ;
Dor-Hefetz, E .
FEMS YEAST RESEARCH, 2003, 4 (01) :7-13
[10]  
Herzberg MC, 2000, PERSISTENT BACTERIAL, P470