Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis.
Programmed cell death is a gene-directed process involved in the development and homeostasis of multicellular organisms. The most common mode of programmed cell death is apoptosis, which is characterized by a stereotypical set of biochemical and morphological hallmarks. Here we report that Escherichia coli also exhibit characteristic markers of apoptosis-including phosphatidylserine exposure, chromosome condensation, and DNA fragmentation-when faced with cell death-triggering stress, namely bactericidal antibiotic treatment. Notably, we also provide proteomic and genetic evidence for the ability of multifunctional RecA to bind peptide sequences that serve as substrates for eukaryotic caspases, and regulation of this phenotype by the protease, ClpXP, under conditions of cell death. Our findings illustrate that prokaryotic organisms possess mechanisms to dismantle and mark dying cells in response to diverse noxious stimuli and suggest that elaborate, multilayered proteolytic regulation of these features may have evolved in eukaryotes to harness and exploit their deadly potential.
Howard Hughes Medical Institute, Boston University, Boston, MA 02215, USA.
Daniel J
DJ
Dwyer
Diogo M
DM
Camacho
Michael A
MA
Kohanski
Jarred M
JM
Callura
James J
JJ
Collins
D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D002876:Chromosomes, Bacterial / Q000187:drug effects; D053938:DNA Fragmentation; D049071:Endopeptidase Clp / Q000502:physiology; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000502:physiology; D005839:Gentamicins / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D009643:Norfloxacin / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000032:analysis; D011938:Rec A Recombinases / Q000378:metabolism / Q000502:physiology; D013014:SOS Response, Genetics / Q000187:drug effects; D013312:Stress, Physiological; D013379:Substrate Specificity
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005839:Gentamicins; D010718:Phosphatidylserines; D000667:Ampicillin; D011938:Rec A Recombinases; C483572:ClpP protease, E coli; D049071:Endopeptidase Clp; D020169:Caspases; D009643:Norfloxacin