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A ParDE-family Toxin Antitoxin System In Major Resistance Plasmids Of Enterobacteriaceae Confers Antibiotic And Heat Tolerance

M. Kamruzzaman, J. Iredell
Published 2019 · Biology, Medicine

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Toxin-antitoxin (TA) systems were initially discovered as plasmid addiction systems on low-copy-number plasmids. Thousands of TA loci have since been identified on chromosomes, plasmids and mobile elements in bacteria and archaea with diverse roles in bacterial physiology and in maintenance of genetic elements. Here, we identified and characterised a plasmid mediated type II TA system in Enterobacteriaceae as a member of the ParDE super family. This system (hereafter, ParDEI) is distributed among IncI and IncF-type antibiotic resistance and virulence plasmids found in avian and human-source Escherichia coli and Salmonella. It is found that ParDEI is a plasmid stability and stress response module that increases tolerance of aminoglycoside, quinolone and β-lactam antibiotics in E. coli by ~100–1,000-fold, and thus to levels beyond those achievable in the course of antibiotic therapy for human infections. ParDEI also confers a clear survival advantage at 42 °C and expression of the ParEI toxin in trans induces the SOS response, inhibits cell division and promotes biofilm formation. This transmissible high-level antibiotic tolerance is likely to be an important factor in the success of the IncI and IncF plasmids which carry it and the important pathogens in which these are resident.
This paper references
A toxin antitoxin system promotes the maintenance of the IncA/Cmobilizable Salmonella
K. T. Huguet (2016)
10.1126/SCIENCE.1088157
Toxins-Antitoxins: Plasmid Maintenance, Programmed Cell Death, and Cell Cycle Arrest
F. Hayes (2003)
still more questions than answers? Nat
N. Q. Balaban (2013)
10.1073/pnas.1121217109
Additional role for the ccd operon of F-plasmid as a transmissible persistence factor
Arti Tripathi (2012)
10.1128/mBio.00971-17
Quinolone Resistance Reversion by Targeting the SOS Response
E. Recacha (2017)
10.1111/1462-2920.12373
Toxin GhoT of the GhoT/GhoS toxin/antitoxin system damages the cell membrane to reduce adenosine triphosphate and to reduce growth under stress.
Hsin-Yao Cheng (2014)
10.1128/mBio.01964-17
Prophages and Growth Dynamics Confound Experimental Results with Antibiotic-Tolerant Persister Cells
A. Harms (2017)
10.1006/METH.2001.1262
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
K. Livak (2001)
10.1038/nrmicro3076
A problem of persistence: still more questions than answers?
N. Balaban (2013)
10.1111/j.1365-2958.2010.07207.x
Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE‐family toxin–antitoxin systems
A. Fiebig (2010)
10.1128/mBio.00640-18
Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
F. Goormaghtigh (2018)
10.1093/femsre/fuw022
Toxin-antitoxins and bacterial virulence.
Damián Lobato-Márquez (2016)
10.1186/1471-2199-4-11
Lambda Red-mediated recombinogenic engineering of enterohemorrhagic and enteropathogenic E. coli
K. Murphy (2003)
10.1128/JB.155.2.768-775.1983
hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis.
H. Moyed (1983)
10.1371/journal.ppat.1002954
Toxin-Antitoxin Systems Are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli
J. Norton (2012)
10.1016/S0092-8674(02)01248-5
The Bacterial Toxin RelE Displays Codon-Specific Cleavage of mRNAs in the Ribosomal A Site
K. Pedersen (2003)
10.1128/JB.01465-08
Toxin-antitoxin systems in Escherichia coli influence biofilm formation through YjgK (TabA) and fimbriae.
Y. Kim (2009)
10.1073/pnas.251327898
RelE, a global inhibitor of translation, is activated during nutritional stress
S. Christensen (2001)
10.1128/JB.01185-10
The three vibrio cholerae chromosome II-encoded ParE toxins degrade chromosome I following loss of chromosome II.
J. Yuan (2011)
10.1128/AAC.02773-14
Complete Sequencing of IncI1 Sequence Type 2 Plasmid pJIE512b Indicates Mobilization of blaCMY-2 from an IncA/C Plasmid
Kaitlin A. Tagg (2014)
10.3389/fmicb.2016.02134
Persistent Persister Misperceptions
Jun-Seob Kim (2016)
10.1038/srep32285
A toxin antitoxin system promotes the maintenance of the IncA/C-mobilizable Salmonella Genomic Island 1
Kévin T. Huguet (2016)
10.1128/JB.186.24.8172-8180.2004
Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli.
I. Keren (2004)
10.1016/S0966-842X(00)01913-2
Mechanisms of biofilm resistance to antimicrobial agents.
T. Mah (2001)
10.1073/pnas.052694299
Quorum-sensing regulators control virulence gene expression in Vibrio cholerae
J. Zhu (2002)
10.1007/s00253-016-7648-8
Persisters—as elusive as ever
N. Kaldalu (2016)
Plasmid - mediated resistance in Enterobacteriaceae : changing landscape and implications for therapy
C. Schultsz (2012)
10.1016/S0378-1097(03)00856-5
Persister cells and tolerance to antimicrobials.
I. Keren (2004)
10.1038/nrmicro1147
Prokaryotic toxin–antitoxin stress response loci
K. Gerdes (2005)
10.1073/pnas.1100186108
Bacterial persistence by RNA endonucleases
Etienne Maisonneuve (2011)
10.1126/science.7846528
Programmed cell death in bacterial populations
M. Yarmolinsky (1995)
10.1093/bioinformatics/16.4.404
The PSIPRED protein structure prediction server
L. McGuffin (2000)
Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔCT) Method
K. J. Livak (2001)
10.1128/AAC.01707-08
Resistance Plasmid Families in Enterobacteriaceae
A. Carattoli (2009)
10.1074/jbc.M113.510511
MazF-induced Growth Inhibition and Persister Generation in Escherichia coli *
Arti Tripathi (2013)
10.1006/JMBI.1994.1207
The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss.
R. Roberts (1994)
10.1371/journal.pgen.1000439
A Toxin–Antitoxin System Promotes the Maintenance of an Integrative Conjugative Element
Rachel A. F. Wozniak (2009)
plasmid maintenance, programmed cell death, and cell cycle arrest
Hayes (2003)
Metagenomics And Its Applications In Agriculture Biomedicine And Environmental Studies
L. Bieber (2016)
10.1128/AEM.05068-11
Toxin-Antitoxin Systems Influence Biofilm and Persister Cell Formation and the General Stress Response
Xiaoxue Wang (2011)
10.3382/ps.2012-02504
Effect of hot water spray on broiler carcasses for reduction of loosely attached, intermediately attached, and tightly attached pathogenic (Salmonella and Campylobacter) and mesophilic aerobic bacteria.
L. Zhang (2013)
10.1128/AAC.00420-15
Relative Strengths of Promoters Provided by Common Mobile Genetic Elements Associated with Resistance Gene Expression in Gram-Negative Bacteria
M. Kamruzzaman (2015)
changing landscape and implications for therapy
C. Schultsz (2012)
10.1016/j.molmed.2012.03.003
Carbapenem resistance in Enterobacteriaceae: here is the storm!
P. Nordmann (2012)
10.1128/JB.186.7.2123-2133.2004
Plasmid evolution and interaction between the plasmid addiction stability systems of two related broad-host-range IncQ-like plasmids.
S. Deane (2004)
10.1016/j.molcel.2015.05.011
Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.
N. Verstraeten (2015)
10.1126/science.aaf4268
Mechanisms of bacterial persistence during stress and antibiotic exposure
A. Harms (2016)
10.1111/j.1365-2958.2007.05613.x
Chromosomal toxin–antitoxin loci can diminish large‐scale genome reductions in the absence of selection
S. Szekeres (2007)
10.1021/cr400656f
Disorder- and dynamics-based regulatory mechanisms in toxin-antitoxin modules.
R. Loris (2014)
10.1128/AEM.00598-11
Population Dynamics of Salmonella enterica Serotypes in Commercial Egg and Poultry Production
S. Foley (2011)
Toxin-antitoxin systems: Biology, identification, and application. Mobile genetic elements 3, e26219
S J Unterholzner (2013)
10.1016/J.FOODCONT.2016.04.006
An overview of Salmonella thermal destruction during food processing and preparation
N. Jarvis (2016)
10.3389/fmicb.2017.00191
Commentary: What Is the Link between Stringent Response, Endoribonuclease Encoding Type II Toxin-Antitoxin Systems and Persistence?
L. Van Melderen (2017)
10.1089/fpd.2014.1824
Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS response in Escherichia coli O104:H4.
Sukayna M. Fadlallah (2015)
10.1371/journal.pbio.1000317
Ciprofloxacin Causes Persister Formation by Inducing the TisB toxin in Escherichia coli
Tobias Dörr (2010)
10.1128/JB.00436-12
Global expression profile of biofilm resistance to antimicrobial compounds in the plant-pathogenic bacterium Xylella fastidiosa reveals evidence of persister cells.
L. S. Muranaka (2012)
Resistance plasmid families in
A. Carattoli (2009)
10.1371/journal.pone.0135696
Functional RelBE-Family Toxin-Antitoxin Pairs Affect Biofilm Maturation and Intestine Colonization in Vibrio cholerae
Y. Wang (2015)
10.1128/JB.01395-08
Genetics and proteomics of Aeromonas salmonicida lipopolysaccharide core biosynthesis.
N. Jiménez (2009)
Biology, identification, and application
S. J. Unterholzner (2013)
Toxin - antitoxin systems : Biology , identification , and application
S. J. Unterholzner (2013)
10.1371/journal.pone.0172913
Plasmid interference for curing antibiotic resistance plasmids in vivo
M. Kamruzzaman (2017)
10.3389/fmicb.2016.01882
What Is the Link between Stringent Response, Endoribonuclease Encoding Type II Toxin–Antitoxin Systems and Persistence?
B. C. M. Ramisetty (2016)
10.1099/jmm.0.030932-0
Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies.
M. Fauvart (2011)
10.1016/j.cell.2009.11.015
The Structural Basis for mRNA Recognition and Cleavage by the Ribosome-Dependent Endonuclease RelE
Cajetan Neubauer (2009)
10.1046/j.1365-2958.2003.03512.x
RelE toxins from Bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA
S. Christensen (2003)
10.1038/nature13469
Optimization of lag time underlies antibiotic tolerance in evolved bacterial populations
O. Fridman (2014)
10.1016/j.resmic.2009.03.001
Cross-talk mechanisms in biofilm formation and responses to environmental and physiological stress in Escherichia coli.
P. Landini (2009)
10.1038/nrmicro1445
Non-inherited antibiotic resistance
B. Levin (2006)
10.3389/fmicb.2017.00840
MqsR/MqsA Toxin/Antitoxin System Regulates Persistence and Biofilm Formation in Pseudomonas putida KT2440
Chenglong Sun (2017)
here is the storm! Trends Mol
P. Nordmann (2012)
10.1099/00221287-72-3-543
R factors from Proteus rettgeri.
J. N. Coetzee (1972)
10.1016/j.jmb.2019.03.019
Clarifying the Link between Toxin-Antitoxin Modules and Bacterial Persistence.
S. Ronneau (2019)
10.1128/JB.177.14.4121-4130.1995
Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter.
L. M. Guzmán (1995)
10.1146/annurev-micro-092611-150159
Bacterial persistence and toxin-antitoxin loci.
K. Gerdes (2012)
10.1021/bi902133s
A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex.
Kevin M. Dalton (2010)
10.1128/mBio.00354-17
Tolerant, Growing Cells from Nutrient Shifts Are Not Persister Cells
Jun-Seob Kim (2017)
10.1093/JAC/DKL393
Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin.
G. French (2006)
10.1128/JB.151.1.222-228.1982
Genetic and molecular characterization of Tn21, a multiple resistance transposon from R100.1.
F. de la Cruz (1982)
clinical relevance and perspectives on antipersister therapies
M. Fauvart (2011)
10.1093/molbev/msw054
MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.
S. Kumar (2016)
10.1046/j.1365-2958.2002.02921.x
ParE toxin encoded by the broad‐host‐range plasmid RK2 is an inhibitor of Escherichia coli gyrase
Y. Jiang (2002)
10.1146/annurev-genet-110410-132412
Toxin-antitoxin systems in bacteria and archaea.
Yoshihiro Yamaguchi (2011)
10.1371/journal.pgen.1003144
Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin
Steve Bernier (2013)



This paper is referenced by
10.1101/2020.03.06.980490
Specialised functions of two common plasmid mediated toxin-antitoxin systems, ccdAB and pemIK, in Enterobacteriaceae
Alma Y. Wu (2020)
10.3390/toxins12060422
Evaluating the Potential for Cross-Interactions of Antitoxins in Type II TA Systems
Chih-Han Tu (2020)
10.1128/AAC.02385-19
Comparative Genomic Analysis of Third-Generation-Cephalosporin-Resistant Escherichia coli Harboring the blaCMY-2-Positive IncI1 Group, IncB/O/K/Z, and IncC Plasmids Isolated from Healthy Broilers in Japan
Takahiro Shirakawa (2020)
10.3390/microorganisms7110554
Prevalence, Distribution, and Phylogeny of Type Two Toxin-Antitoxin Genes Possessed by Cronobacter Species where C. sakazakii Homologs Follow Sequence Type Lineages
Samantha Finkelstein (2019)
10.3390/toxins12090566
Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK
I. Bleriot (2020)
10.1371/journal.pone.0230652
Specialised functions of two common plasmid mediated toxin-antitoxin systems, ccdAB and pemIK, in Enterobacteriaceae
Alma Y. Wu (2020)
10.20944/preprints202007.0579.v1
Whole Transcriptomic Analysis of Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella Pneumoniae Producers of Carbapenemase
I. Bleriot (2020)
10.1371/journal.pone.0233945
The transcriptome of Listeria monocytogenes during co-cultivation with cheese rind bacteria suggests adaptation by induction of ethanolamine and 1,2-propanediol catabolism pathway genes
J. Anast (2020)
10.1099/mgen.0.000372
Identification of integrative and conjugative elements in pathogenic and commensal Neisseriaceae species via genomic distributions of DNA uptake sequence dialects
A. Hughes-Games (2020)
10.1101/2020.05.18.101832
The transcriptome of Listeria monocytogenes during co-cultivation with cheese rind bacteria suggests adaptation by induction of ethanolamine and 1,2-propanediol catabolism pathway genes
J. Anast (2020)
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