<i>mazEF-</i>mediated programmed cell death in bacteria: “What is this?”

Ramisetty, Bhaskar Chandra Mohan; Natarajan, Bhargavi; Santhosh, Ramachandran Sarojini

doi:10.3109/1040841x.2013.804030

Cited by 49 publications

(36 citation statements)

References 108 publications

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“…This indicates that increases in polyamine concentration and some regulation of translation in stationary phase might be a consequence of MraZ activity. These differences in gene expression between an mraZ null mutant and the isogenic WT parent suggest that MraZ might have a role in cell adaptation or survival in suboptimal environments or under suboptimal growth conditions, as has been proposed for the MazEF toxin-antitoxin system (74,75).…”

Section: Discussionmentioning

confidence: 81%

The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli

Eraso¹,

Markillie²,

Mitchell³

et al. 2014

Journal of Bacteriology

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The mraZ and mraW genes are highly conserved in bacteria, both in sequence and in their position at the head of the division and cell wall (dcw) gene cluster. Located directly upstream of the mraZ gene, the P mra promoter drives the transcription of mraZ and mraW, as well as many essential cell division and cell wall genes, but no regulator of P mra has been found to date. Although MraZ has structural similarity to the AbrB transition state regulator and the MazE antitoxin and MraW is known to methylate the 16S rRNA, mraZ and mraW null mutants have no detectable phenotypes. Here we show that overproduction of Escherichia coli MraZ inhibited cell division and was lethal in rich medium at high induction levels and in minimal medium at low induction levels. Co-overproduction of MraW suppressed MraZ toxicity, and loss of MraW enhanced MraZ toxicity, suggesting that MraZ and MraW have antagonistic functions. MraZ-green fluorescent protein localized to the nucleoid, suggesting that it binds DNA. Consistent with this idea, purified MraZ directly bound a region of DNA containing three direct repeats between P mra and the mraZ gene. Excess MraZ reduced the expression of an mraZ-lacZ reporter, suggesting that MraZ acts as a repressor of P mra , whereas a DNA-binding mutant form of MraZ failed to repress expression. Transcriptome sequencing (RNA-seq) analysis suggested that MraZ also regulates the expression of genes outside the dcw cluster. In support of this, purified MraZ could directly bind to a putative operator site upstream of mioC, one of the repressed genes identified by RNA-seq.

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Section: Discussionmentioning

confidence: 81%

The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli

Eraso¹,

Markillie²,

Mitchell³

et al. 2014

Journal of Bacteriology

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“…Under various stress stimuli (DNA damage, starvation, the presence of antibiotics or free radicals in the environment, high temperature, oxidative or osmotic shock, entrance into stationary phase, quorum sensing, or infecting phages), the toxins can be activated, often as a result of the degradation of antitoxins by stress-induced proteases or of the induction of toxin transcription. Depending on the nature of the stress and of the activated TA system(s), toxins can provoke altruistic programmed cell death to either release nutrients for other cells (226) or stop an infection (232), induce biofilm formation (221), arrest cell growth until improvement of the environmental conditions (238), or differentiate a subpopulation of cells into persisters (multidrug-resistant bacteria in a dormant state) (239). These stress responses can be determined by TA systems controlling DNA replication or the regulation of global or specific gene expression (240,241).…”

Section: Genetic Elements Controlling the Stability Of Mobile Elementsmentioning

confidence: 99%

Bacterial Genome Instability

Darmon

Leach

2014

Microbiol Mol Biol Rev

345

289

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SUMMARY Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease.

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“…Secondly, it is highly improbable that we can obtain relA + derivatives of MC4100 and MC4100DmazEF strains as described by the PCD proponents [14,51]. Thirdly, the concept of PCD, wherein the majority of the cells of the population die, is probably counterproductive for the goal of spatiotemporal propagation [14]. Paradoxically, according to the proposed PCD, it is better for bacteria not to harbour mazEF TAs.…”

Section: Functions Of Chromosomal Type II Tasmentioning

confidence: 99%

“…Firstly, the strains are not isogenic and seem to have numerous problems, including several deletions of the adjacent genes [44,49,50]. Secondly, it is highly improbable that we can obtain relA + derivatives of MC4100 and MC4100DmazEF strains as described by the PCD proponents [14,51]. Thirdly, the concept of PCD, wherein the majority of the cells of the population die, is probably counterproductive for the goal of spatiotemporal propagation [14].…”

Section: Functions Of Chromosomal Type II Tasmentioning

confidence: 99%

“…At least with regard to plasmid-borne TAs, most researchers agree that TAs are 'addiction systems' which reduce the proportion of cells cured of TA-encoding-plasmids by a phenomenon referred to as post-segregational killing (PSK) [11,12]. Proposed chromosomal TA-dependent phenotypes include persistence [4,13], bacterial programmed cell death (PCD) [14][15][16], biofilm formation [17][18][19] and antiaddiction modules [6,20]. Because of the implications of the above clinical phenomena, TAs have been proposed as molecular targets for drug development [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Endoribonuclease type II toxin–antitoxin systems: functional or selfish?

Ramisetty

Santhosh

2017

Microbiology

Self Cite

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Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids. However, the programmed cell death and persistence hypotheses have been challenged because of conceptual, methodological and/or strain issues. In an alternative view, chromosomal TAs seem to be retained by virtue of addiction at two levels: via a poisonantidote combination (TA proteins) and via transcriptional reprogramming of the downstream core gene (due to integration). Any perturbation in the chromosomal TA operons could cause fitness loss due to polar effects on the downstream genes and hence be detrimental under natural conditions. The endoribonucleases encoding chromosomal TAs are most likely selfish DNA as they are retained by bacterial genomes, even though TAs do not confer a direct advantage via the TA proteins. TAs are likely used by various replicons as 'genetic arms' that allow the maintenance of themselves and associated genetic elements. TAs seem to be the 'selfish arms' that make the best use of the 'arms race' between bacterial genomes and plasmids.

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mazEF-mediated programmed cell death in bacteria: “What is this?”

Cited by 49 publications

References 108 publications

The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli

The Highly Conserved MraZ Protein Is a Transcriptional Regulator in Escherichia coli

Bacterial Genome Instability

Endoribonuclease type II toxin–antitoxin systems: functional or selfish?

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