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Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli

BACKGROUND: Bacterial toxin-antitoxin (TA) systems are formed by potent regulatory or suicide factors (toxins) and their short-lived inhibitors (antitoxins). Antitoxins are DNA-binding proteins and auto-repress transcription of TA operons. Transcription of multiple TA operons is activated in tempora...

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Autores principales: Kasari, Villu, Mets, Toomas, Tenson, Tanel, Kaldalu, Niilo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598666/
https://www.ncbi.nlm.nih.gov/pubmed/23432955
http://dx.doi.org/10.1186/1471-2180-13-45
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author Kasari, Villu
Mets, Toomas
Tenson, Tanel
Kaldalu, Niilo
author_facet Kasari, Villu
Mets, Toomas
Tenson, Tanel
Kaldalu, Niilo
author_sort Kasari, Villu
collection PubMed
description BACKGROUND: Bacterial toxin-antitoxin (TA) systems are formed by potent regulatory or suicide factors (toxins) and their short-lived inhibitors (antitoxins). Antitoxins are DNA-binding proteins and auto-repress transcription of TA operons. Transcription of multiple TA operons is activated in temporarily non-growing persister cells that can resist killing by antibiotics. Consequently, the antitoxin levels of persisters must have been dropped and toxins are released of inhibition. RESULTS: Here, we describe transcriptional cross-activation between different TA systems of Escherichia coli. We find that the chromosomal relBEF operon is activated in response to production of the toxins MazF, MqsR, HicA, and HipA. Expression of the RelE toxin in turn induces transcription of several TA operons. We show that induction of mazEF during amino acid starvation depends on relBE and does not occur in a relBEF deletion mutant. Induction of TA operons has been previously shown to depend on Lon protease which is activated by polyphospate accumulation. We show that transcriptional cross-activation occurs also in strains deficient for Lon, ClpP, and HslV proteases and polyphosphate kinase. Furthermore, we find that toxins cleave the TA mRNA in vivo, which is followed by degradation of the antitoxin-encoding fragments and selective accumulation of the toxin-encoding regions. We show that these accumulating fragments can be translated to produce more toxin. CONCLUSION: Transcriptional activation followed by cleavage of the mRNA and disproportionate production of the toxin constitutes a possible positive feedback loop, which can fire other TA systems and cause bistable growth heterogeneity. Cross-interacting TA systems have a potential to form a complex network of mutually activating regulators in bacteria.
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spelling pubmed-35986662013-03-16 Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli Kasari, Villu Mets, Toomas Tenson, Tanel Kaldalu, Niilo BMC Microbiol Research Article BACKGROUND: Bacterial toxin-antitoxin (TA) systems are formed by potent regulatory or suicide factors (toxins) and their short-lived inhibitors (antitoxins). Antitoxins are DNA-binding proteins and auto-repress transcription of TA operons. Transcription of multiple TA operons is activated in temporarily non-growing persister cells that can resist killing by antibiotics. Consequently, the antitoxin levels of persisters must have been dropped and toxins are released of inhibition. RESULTS: Here, we describe transcriptional cross-activation between different TA systems of Escherichia coli. We find that the chromosomal relBEF operon is activated in response to production of the toxins MazF, MqsR, HicA, and HipA. Expression of the RelE toxin in turn induces transcription of several TA operons. We show that induction of mazEF during amino acid starvation depends on relBE and does not occur in a relBEF deletion mutant. Induction of TA operons has been previously shown to depend on Lon protease which is activated by polyphospate accumulation. We show that transcriptional cross-activation occurs also in strains deficient for Lon, ClpP, and HslV proteases and polyphosphate kinase. Furthermore, we find that toxins cleave the TA mRNA in vivo, which is followed by degradation of the antitoxin-encoding fragments and selective accumulation of the toxin-encoding regions. We show that these accumulating fragments can be translated to produce more toxin. CONCLUSION: Transcriptional activation followed by cleavage of the mRNA and disproportionate production of the toxin constitutes a possible positive feedback loop, which can fire other TA systems and cause bistable growth heterogeneity. Cross-interacting TA systems have a potential to form a complex network of mutually activating regulators in bacteria. BioMed Central 2013-02-21 /pmc/articles/PMC3598666/ /pubmed/23432955 http://dx.doi.org/10.1186/1471-2180-13-45 Text en Copyright ©2013 Kasari et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kasari, Villu
Mets, Toomas
Tenson, Tanel
Kaldalu, Niilo
Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title_full Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title_fullStr Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title_full_unstemmed Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title_short Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli
title_sort transcriptional cross-activation between toxin-antitoxin systems of escherichia coli
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598666/
https://www.ncbi.nlm.nih.gov/pubmed/23432955
http://dx.doi.org/10.1186/1471-2180-13-45
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