Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>

ABSTRACT Toxin-antitoxin (TA) systems are broadly distributed modules whose biological roles remain mostly unknown. The mqsRA system is a noncanonical TA system in which the toxin and antitoxins genes are organized in operon but with the particularity that the toxin gene precedes that of the antitox...

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Main Authors: Nathan Fraikin, Clothilde J. Rousseau, Nathalie Goeders, Laurence Van Melderen
Format: Article
Language:English
Published: American Society for Microbiology 2019-12-01
Series:mBio
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mBio.02678-19
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author Nathan Fraikin
Clothilde J. Rousseau
Nathalie Goeders
Laurence Van Melderen
author_facet Nathan Fraikin
Clothilde J. Rousseau
Nathalie Goeders
Laurence Van Melderen
author_sort Nathan Fraikin
collection DOAJ
description ABSTRACT Toxin-antitoxin (TA) systems are broadly distributed modules whose biological roles remain mostly unknown. The mqsRA system is a noncanonical TA system in which the toxin and antitoxins genes are organized in operon but with the particularity that the toxin gene precedes that of the antitoxin. This system was shown to regulate global processes such as resistance to bile salts, motility, and biofilm formation. In addition, the MqsA antitoxin was shown to be a master regulator that represses the transcription of the csgD, cspD, and rpoS global regulator genes, thereby displaying a pleiotropic regulatory role. Here, we identified two promoters located in the toxin sequence driving the constitutive expression of mqsA, allowing thereby excess production of the MqsA antitoxin compared to the MqsR toxin. Our results show that both antitoxin-specific and operon promoters are not regulated by stresses such as amino acid starvation, oxidative shock, or bile salts. Moreover, we show that the MqsA antitoxin is not a global regulator as suggested, since the expression of csgD, cspD and rpoS is similar in wild-type and ΔmqsRA mutant strains. Moreover, these two strains behave similarly in terms of biofilm formation and sensitivity to oxidative stress or bile salts. IMPORTANCE There is growing controversy regarding the role of chromosomal toxin-antitoxin systems in bacterial physiology. mqsRA is a peculiar toxin-antitoxin system, as the gene encoding the toxin precedes that of the antitoxin. This system was previously shown to play a role in stress response and biofilm formation. In this work, we identified two promoters specifically driving the constitutive expression of the antitoxin, thereby decoupling the expression of antitoxin from the toxin. We also showed that mqsRA contributes neither to the regulation of biofilm formation nor to the sensitivity to oxidative stress and bile salts. Finally, we were unable to confirm that the MqsA antitoxin is a global regulator. Altogether, our data are ruling out the involvement of the mqsRA system in Escherichia coli regulatory networks.
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spelling doaj.art-70517d750ee24d10acdc10ae690ef0012022-12-21T20:07:15ZengAmerican Society for MicrobiologymBio2150-75112019-12-0110610.1128/mBio.02678-19Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>Nathan Fraikin0Clothilde J. Rousseau1Nathalie Goeders2Laurence Van Melderen3Cellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Gosselies, BelgiumCellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Gosselies, BelgiumCellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Gosselies, BelgiumCellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Gosselies, BelgiumABSTRACT Toxin-antitoxin (TA) systems are broadly distributed modules whose biological roles remain mostly unknown. The mqsRA system is a noncanonical TA system in which the toxin and antitoxins genes are organized in operon but with the particularity that the toxin gene precedes that of the antitoxin. This system was shown to regulate global processes such as resistance to bile salts, motility, and biofilm formation. In addition, the MqsA antitoxin was shown to be a master regulator that represses the transcription of the csgD, cspD, and rpoS global regulator genes, thereby displaying a pleiotropic regulatory role. Here, we identified two promoters located in the toxin sequence driving the constitutive expression of mqsA, allowing thereby excess production of the MqsA antitoxin compared to the MqsR toxin. Our results show that both antitoxin-specific and operon promoters are not regulated by stresses such as amino acid starvation, oxidative shock, or bile salts. Moreover, we show that the MqsA antitoxin is not a global regulator as suggested, since the expression of csgD, cspD and rpoS is similar in wild-type and ΔmqsRA mutant strains. Moreover, these two strains behave similarly in terms of biofilm formation and sensitivity to oxidative stress or bile salts. IMPORTANCE There is growing controversy regarding the role of chromosomal toxin-antitoxin systems in bacterial physiology. mqsRA is a peculiar toxin-antitoxin system, as the gene encoding the toxin precedes that of the antitoxin. This system was previously shown to play a role in stress response and biofilm formation. In this work, we identified two promoters specifically driving the constitutive expression of the antitoxin, thereby decoupling the expression of antitoxin from the toxin. We also showed that mqsRA contributes neither to the regulation of biofilm formation nor to the sensitivity to oxidative stress and bile salts. Finally, we were unable to confirm that the MqsA antitoxin is a global regulator. Altogether, our data are ruling out the involvement of the mqsRA system in Escherichia coli regulatory networks.https://journals.asm.org/doi/10.1128/mBio.02678-19MqsRMqsATA systemstress adaptationbiofilmglobal regulation
spellingShingle Nathan Fraikin
Clothilde J. Rousseau
Nathalie Goeders
Laurence Van Melderen
Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
mBio
MqsR
MqsA
TA system
stress adaptation
biofilm
global regulation
title Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
title_full Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
title_fullStr Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
title_full_unstemmed Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
title_short Reassessing the Role of the Type II MqsRA Toxin-Antitoxin System in Stress Response and Biofilm Formation: <italic toggle="yes">mqsA</italic> Is Transcriptionally Uncoupled from <italic toggle="yes">mqsR</italic>
title_sort reassessing the role of the type ii mqsra toxin antitoxin system in stress response and biofilm formation italic toggle yes mqsa italic is transcriptionally uncoupled from italic toggle yes mqsr italic
topic MqsR
MqsA
TA system
stress adaptation
biofilm
global regulation
url https://journals.asm.org/doi/10.1128/mBio.02678-19
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