A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>

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 multicel...

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Autores principales: Liselot Dewachter, Natalie Verstraeten, Daniel Monteyne, Cyrielle Ines Kint, Wim Versées, David Pérez-Morga, Jan Michiels, Maarten Fauvart
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Publicado: American Society for Microbiology 2015
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spelling oai:doaj.org-article:436fd5868fef49c7859ec243143231682021-11-15T15:41:24ZA Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mBio.01935-152150-7511https://doaj.org/article/436fd5868fef49c7859ec243143231682015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01935-15https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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.Liselot DewachterNatalie VerstraetenDaniel MonteyneCyrielle Ines KintWim VerséesDavid Pérez-MorgaJan MichielsMaarten FauvartAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Liselot Dewachter
Natalie Verstraeten
Daniel Monteyne
Cyrielle Ines Kint
Wim Versées
David Pérez-Morga
Jan Michiels
Maarten Fauvart
A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
description 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. IMPORTANCE 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.
format article
author Liselot Dewachter
Natalie Verstraeten
Daniel Monteyne
Cyrielle Ines Kint
Wim Versées
David Pérez-Morga
Jan Michiels
Maarten Fauvart
author_facet Liselot Dewachter
Natalie Verstraeten
Daniel Monteyne
Cyrielle Ines Kint
Wim Versées
David Pérez-Morga
Jan Michiels
Maarten Fauvart
author_sort Liselot Dewachter
title A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
title_short A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort single-amino-acid substitution in obg activates a new programmed cell death pathway in <named-content content-type="genus-species">escherichia coli</named-content>
publisher American Society for Microbiology
publishDate 2015
url https://doaj.org/article/436fd5868fef49c7859ec24314323168
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