Programmed Cell Death in
            <i>Escherichia coli</i>
            : Some Antibiotics Can Trigger
            <i>mazEF</i>
            Lethality

Sat, Boaz; Hazan, Ronen; Fisher, Tova; Khaner, Hanita; Glaser, Gad; Engelberg‐Kulka, Hanna

doi:10.1128/jb.183.6.2041-2045.2001

Cited by 218 publications

(205 citation statements)

References 27 publications

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“…The E. coli MazF protein cleaves both mRNA and 16S ribosomal RNA, and is proposed to generate a subpopulation of stress ribosomes, thereby enabling the translation of leaderless transcripts 19 . MazEF systems in E. coli are activated on exposure to numerous stress conditions in an extracellular death factor-dependent manner [20][21][22] . In E. coli, MazF-mediated drug-induced persistence is RecA independent, but dependent on ClpP and Lon proteases 23 .…”

mentioning

confidence: 99%

MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

et al. 2015

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Toxin-antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role in physiology and virulence. Nine of these TA systems belong to the mazEF family, encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce bacteriostasis. The construction of various single-, double-and triple-mutant Mtb strains reveals that these MazF ribonucleases contribute synergistically to the ability of Mtb to adapt to conditions such as oxidative stress, nutrient depletion and drug exposure. Moreover, guinea pigs infected with the triple-mutant strain exhibits significantly reduced bacterial loads and pathological damage in infected tissues in comparison with parental strain-infected guinea pigs. The present study highlights the importance of MazF ribonucleases in Mtb stress adaptation, drug tolerance and virulence.

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confidence: 99%

MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

et al. 2015

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“…This is attributed to the formation of more resistant forms of cell structure as a defense against low temperature, which includes low metabolism rates and nutrient uptake. As it seems, either reparation of photo-induced damage or, along with delayed metabolic action, a delayed programmed cell death [48] triggered by light exposure is observed.…”

Section: Resultsmentioning

confidence: 99%

Monitoring the post-irradiation E. coli survival patterns in environmental water matrices: Implications in handling solar disinfected wastewater

Giannakis

Gamo

Darakas

et al. 2014

Chemical Engineering Journal

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In this study, simulated solar disinfection of secondary effluent was followed by dark storage at different temperatures or different receiving water matrices. E. coli illumination was followed by 3-day monitoring of the bacterial population and its adaptation in different temperature conditions in the dark. The subsequent survival was linked to the dose received during exposure to light, and results were obtained on the environmentally induced prolongation of survival, maintenance of population or excessive growth, at 4, 20 and 37˚C, respectively. An additional set of experiments at 20˚C was subjected to dilution in E. coli-free synthetic wastewater, water from Lake Leman, (synthetic) seawater and Mili-Q water. Post-irradiation NOTICE: this is the author's version of a work that was accepted for publication in Chemical Engineering Journal. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Chemical Engineering Journal [Vol. 253, p. 366-376, October 2014]. DOI: 10.1016DOI: 10. /j.cej.2014 2 monitoring was also conducted, studying 50%, 10% and 1% dilution rates, and the results were attributed to the two parameters of dilution medium and dilution ratio. However, different responses were found based on the acquired dose during pre-treatment. This indicates the importance of the illumination prior to storage, and the preference of bacteria in some matrices over the others. Survival was linked to initial population, dose, dilution and medium; shorter illumination times are to be considered according to the receiving water matrix.

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“…Such TA systems are sometimes referred to as "plasmid addiction" modules [7,8]. The precise role of TA systems encoded by bacterial chromosomes is less clear, but there is evidence that they may serve as stress response elements, as toxin-induced cell death is observed under conditions including high temperatures, DNA damage, oxidative stress [9], thymine starvation [10], and antibiotic treatment [11]. In addition, the transcription of genes from chromosomally encoded TA loci are upregulated during amino acid starvation [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Most proteic TA systems are characterized by two small (8)(9)(10)(11)(12)(13)(14)(15) proteins, a stable toxin and a labile antitoxin, and genes encoding these proteins have been identified on a wide range of bacterial chromosomes and plasmids [4,5]. If both proteins are actively being produced by the bacterial cell, the antitoxin binds the toxin and inhibits its toxic activity.…”

Section: Introductionmentioning

confidence: 99%

A continuous fluorometric assay for the assessment of MazF ribonuclease activity

Wang

Hergenrother

2007

Analytical Biochemistry

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Plasmids maintain themselves in their bacterial host through several different mechanisms, one of which involves the synthesis of plasmid-encoded toxin and antitoxin proteins. When the plasmid is present the antitoxin binds to and neutralizes the toxin. If a plasmid-free daughter cell arises, however, the labile antitoxin is degraded (and not replenished) and the toxin kills the cell from within. These toxin-antitoxin (TA) systems thereby function as post-segregational killing systems, and the disruption of the TA interaction represents an intriguing antibacterial strategy. It was recently discovered that the genes for one particular TA system, MazEF, are ubiquitous on plasmids isolated from clinical vancomycin-resistant enterococci (VRE) strains. It thus appears that small molecule disruptors of the MazEF interaction have potential as antibacterial agents. The MazF toxin protein is known to be a ribonuclease. Unfortunately, traditional methods for the assessment of MazF activity rely on the use of radiolabeled substrates followed by analysis with polyacrylamide gel electrophoresis. Described herein is a simple and convenient continuous assay for the assessment of MazF activity. This assay utilizes an oligonucleotide with a fluorophore on the 5′-end and a quencher on the 3′-end, and processing of this substrate by MazF results in a large increase in the fluorescence signal. Through this assay we have for the first time determined a K M and V max for this enzyme, and have also found that MazF is not inhibited by standard ribonuclease inhibitors. This assay will be useful to those interested in the biochemistry of the MazF family of toxins and the disruption of MazE-MazF.

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Programmed Cell Death in Escherichia coli : Some Antibiotics Can Trigger mazEF Lethality

Cited by 218 publications

References 27 publications

MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

Monitoring the post-irradiation E. coli survival patterns in environmental water matrices: Implications in handling solar disinfected wastewater

A continuous fluorometric assay for the assessment of MazF ribonuclease activity

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