Figure 1. Live/Dead staining of cells expressing Obg*.  Cells expressing Obg* were subjected to Live/Dead staining. Dead cells stain red, while living cells stain green. Expression of Obg* causes the cells to die.

Programmed cell death and cell cycle control in bacteria

Research carried out by Liselot Dewachter, Natalie Verstraeten, Maarten Fauvart

The existence of programmed cell death (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.

Moreover, it was argued that the functions of bacterial programmed cell death might be analogous to its functions in higher eukaryotes, namely the development of multicellular structures and the prolonged preservation of the ‘organism’, the bacterial population.

We discovered that substitution of a single amino acid in the G domain of Obg gives rise to a mutant isoform, Obg*, that when expressed induces rapid cell death in Escherichia coli.

Further investigations into the phenotypic changes and genetic basis of Obg* toxicity revealed that the Obg*-mediated cell death pathway is programmed and differs fundamentally from all other previously described bacterial programmed cell death pathways.

Research into Obg*-mediated programmed cell death can provide more insight into the mechanism and evolution of programmed cell death pathways. More importantly, especially in the light of the looming antibiotic crisis, it may point to a bacterial Achilles heel and can inspire innovative ways of combatting bacterial infections.

Related publications:

Dewachter L., Verstraeten N., Jennes M., Verbeelen T., Biboy J., Monteyne D., Pérez-Morga D., Verstrepen K.J., Vollmer W., Fauvart M., Michiels J. (2017) A mutant isoform of ObgE causes cell death by interfering with cell division. Front. Microbiol. 8:1193 -- PubMed -- PDF

Dewachter L., Herpels P., Verstraeten N., Fauvart M., Michiels J. (2016) Reactive oxygen species do not contribute to ObgE*-mediated programmed cell death. Sci. Rep. 6:33723 -- PubMed -- PDF

Dewachter L., Verstraeten N., Monteyne D., Kint C.I., Versées W., Pérez-Morga D., Michiels J., Fauvart M. (2015) A single-amino acid substitution in Obg activates a new programmed cell death pathway in Escherichia coli. mBio 6:e01935-15. PubMed -- PDF -- cover of the December issue -- Microreview in Microbial Cell

Kint C.I., Verstraeten N., Hofkens J., Fauvart M., Michiels J. (2014) Bacterial Obg proteins: GTPases at the nexus of protein and DNA synthesis. Crit. Rev. Microbiol. 40:207-224 -- PubMed -- PDF

Kint C.I., Verstraeten N., Wens I., Liebens V.R., Hofkens J., Versées W., Fauvart M., Michiels J. (2012). The Escherichia coli GTPase ObgE modulates hydroxyl radical levels in response to DNA replication fork arrest. FEBS J. 279:3692-3704 -- PubMed -- PDF

Verstraeten N., Fauvart M., Versées W., Michiels J. (2011). The universally conserved prokaryotic GTPases. Microbiol. Mol. Biol. Rev. 75:507-542 -- PubMed -- PDF

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