title: A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli.
abstract: Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein--including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing--point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD.
  
  
  OBJECTIVE
  Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development--for example, the disappearance of the interdigital web--and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles' heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways.
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Liselot
authors.initials: L
authors.lastname: Dewachter
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: Verstraeten
authors.affiliation: Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Monteyne
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Cyrielle Ines
authors.initials: CI
authors.lastname: Kint
authors.affiliation: Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium Structural Biology Research Center, VIB, Brussels, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Versées
authors.affiliation: Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Belgium Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Morga
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven-University of Leuven, Leuven, Belgium jan.michiels@biw.kuleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven-University of Leuven, Leuven, Belgium Department of Life Science Technologies, Smart Systems and Emerging Technologies Unit, imec, Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Fauvart
mesh_terms: D019943:Amino Acid Substitution; D017209:Apoptosis; D053938:DNA Fragmentation; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D008564:Membrane Potentials; D050296:Microbial Viability; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010718:Phosphatidylserines / Q000032:analysis
chemical_list: D029968:Escherichia coli Proteins; D050505:Mutant Proteins; D010718:Phosphatidylserines; C491572:ObgE protein, E coli; D020559:Monomeric GTP-Binding Proteins