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PMID: 19325885 Published · ppublish English Journal Article Review

Bacterial toxin-antitoxin systems: more than selfish entities?

PLoS genetics ·Vol. 5 ·No. 3 ·2009-03-00 ·Pages e1000437

Van Melderen L, Saavedra De Bast M

Abstract

Bacterial toxin-antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.

MeSH Terms
Antitoxins/genetics Bacterial Toxins/genetics Escherichia coli Proteins Genome, Bacterial Operon Selection, Genetic
Chemicals
Antitoxins Bacterial Toxins Escherichia coli Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Van Melderen Laurence
Laboratoire de Génétique et Physiologie Bactérienne, IBMM, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium.
Saavedra De Bast Manuel
Conflict of Interest

The authors have declared that no competing interests exist.

References (59)
59 references, click to expand
  1. Small toxic proteins and the antisense RNAs that repress them.
    Microbiol Mol Biol Rev. 2008 Dec;72(4):579-89, Table of Contents PMID: 19052321
  2. Prokaryotic toxin-antitoxin stress response loci.
    Nat Rev Microbiol. 2005 May;3(5):371-82 PMID: 15864262
  3. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis.
    Mol Microbiol. 2003 Nov;50(4):1199-213 PMID: 14622409
  4. Integrons: agents of bacterial evolution.
    Nat Rev Microbiol. 2006 Aug;4(8):608-20 PMID: 16845431
  5. Multiple hok genes on the chromosome of Escherichia coli.
    Mol Microbiol. 1999 Jun;32(5):1090-102 PMID: 10361310
  6. Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.
    Science. 2009 Jan 16;323(5912):396-401 PMID: 19150849
  7. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  8. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?
    J Bacteriol. 2007 Sep;189(17):6101-8 PMID: 17513477
  9. Ectopic overexpression of wild-type and mutant hipA genes in Escherichia coli: effects on macromolecular synthesis and persister formation.
    J Bacteriol. 2006 Jun;188(11):3826-36 PMID: 16707675
  10. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system.
    Mol Microbiol. 2004 Mar;51(6):1705-17 PMID: 15009896
  11. MazF-mediated cell death in Escherichia coli: a point of no return.
    J Bacteriol. 2004 Dec;186(24):8295-300 PMID: 15576778
  12. Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35-amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli.
    Mol Microbiol. 2002 Jul;45(2):333-49 PMID: 12123448
  13. VapC-1 of nontypeable Haemophilus influenzae is a ribonuclease.
    J Bacteriol. 2007 Jul;189(14):5041-8 PMID: 17496075
  14. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family.
    Mol Microbiol. 1998 Aug;29(4):1065-76 PMID: 9767574
  15. Selfish restriction modification genes: resistance of a resident R/M plasmid to displacement by an incompatible plasmid mediated by host killing.
    Biol Chem. 1998 Apr-May;379(4-5):429-36 PMID: 9628334
  16. Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality.
    J Bacteriol. 2001 Mar;183(6):2041-5 PMID: 11222603
  17. MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development.
    Cell. 2008 Jan 11;132(1):55-66 PMID: 18191220
  18. New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system.
    Genome Biol. 2003;4(12):R81 PMID: 14659018
  19. The stable maintenance system pem of plasmid R100: degradation of PemI protein may allow PemK protein to inhibit cell growth.
    J Bacteriol. 1992 Jul;174(13):4205-11 PMID: 1624414
  20. RNA antitoxins.
    Curr Opin Microbiol. 2007 Apr;10(2):117-24 PMID: 17376733
  21. Genetic addiction: selfish gene's strategy for symbiosis in the genome.
    Genetics. 2006 Feb;172(2):1309-23 PMID: 16299387
  22. Functional analysis of putative restriction-modification system genes in the Helicobacter pylori J99 genome.
    Nucleic Acids Res. 2000 Sep 1;28(17):3216-23 PMID: 10954588
  23. Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes and can stabilize plasmids.
    Mol Microbiol. 2006 Oct;62(2):397-411 PMID: 17020579
  24. Genome evolution in bacteria: order beneath chaos.
    Curr Opin Microbiol. 2005 Oct;8(5):572-8 PMID: 16122972
  25. Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells.
    Proc Natl Acad Sci U S A. 1986 May;83(10):3116-20 PMID: 3517851
  26. Lon-dependent proteolysis of CcdA is the key control for activation of CcdB in plasmid-free segregant bacteria.
    Mol Microbiol. 1994 Mar;11(6):1151-7 PMID: 8022284
  27. The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid in an obligate intracellular parasite.
    PLoS Biol. 2005 Aug;3(8):e248 PMID: 15984913
  28. Insertion with long target duplication: a mechanism for gene mobility suggested from comparison of two related bacterial genomes.
    Gene. 2000 Dec 23;259(1-2):99-108 PMID: 11163967
  29. The decay of the chromosomally encoded ccdO157 toxin-antitoxin system in the Escherichia coli species.
    Genetics. 2009 Apr;181(4):1557-66 PMID: 19189956
  30. The balance of driving forces during genome evolution in prokaryotes.
    Genome Res. 2003 Jul;13(7):1589-94 PMID: 12840037
  31. RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA.
    Mol Microbiol. 2003 Jun;48(5):1389-400 PMID: 12787364
  32. RelE, a global inhibitor of translation, is activated during nutritional stress.
    Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14328-33 PMID: 11717402
  33. Crystallization and preliminary X-ray diffraction studies of the epsilonzeta addiction system encoded by Streptococcus pyogenes plasmid pSM19035.
    Acta Crystallogr D Biol Crystallogr. 2001 May;57(Pt 5):745-7 PMID: 11320325
  34. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation.
    J Biol Chem. 2008 Nov 7;283(45):30821-7 PMID: 18757857
  35. Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli.
    J Bacteriol. 2006 Dec;188(24):8360-7 PMID: 17041039
  36. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit.
    Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5885-90 PMID: 18398006
  37. Comparative analysis of superintegrons: engineering extensive genetic diversity in the Vibrionaceae.
    Genome Res. 2003 Mar;13(3):428-42 PMID: 12618374
  38. Chromosomal toxin-antitoxin loci can diminish large-scale genome reductions in the absence of selection.
    Mol Microbiol. 2007 Mar;63(6):1588-605 PMID: 17367382
  39. Programmed cell death in bacterial populations.
    Science. 1995 Feb 10;267(5199):836-7 PMID: 7846528
  40. Evolutionary aspects of whole-genome biology.
    Curr Opin Struct Biol. 2005 Jun;15(3):248-53 PMID: 15963888
  41. Postsegregational killing does not increase plasmid stability but acts to mediate the exclusion of competing plasmids.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12643-8 PMID: 11058151
  42. Repression of small toxic protein synthesis by the Sib and OhsC small RNAs.
    Mol Microbiol. 2008 Dec;70(5):1076-93 PMID: 18710431
  43. Hypothetical functions of toxin-antitoxin systems.
    J Bacteriol. 2007 Sep;189(17):6089-92 PMID: 17616596
  44. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions.
    J Bacteriol. 2004 Jun;186(11):3663-9 PMID: 15150257
  45. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA.
    J Mol Biol. 2003 Sep 26;332(4):809-19 PMID: 12972253
  46. Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes.
    Nucleic Acids Res. 2005 Feb 17;33(3):966-76 PMID: 15718296
  47. Functional interactions between coexisting toxin-antitoxin systems of the ccd family in Escherichia coli O157:H7.
    J Bacteriol. 2007 Apr;189(7):2712-9 PMID: 17259320
  48. Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae.
    J Bacteriol. 2007 Jan;189(2):491-500 PMID: 17085558
  49. Chromosomal toxin-antitoxin systems may act as antiaddiction modules.
    J Bacteriol. 2008 Jul;190(13):4603-9 PMID: 18441063
  50. Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli.
    J Bacteriol. 2004 Dec;186(24):8172-80 PMID: 15576765
  51. A linear pentapeptide is a quorum-sensing factor required for mazEF-mediated cell death in Escherichia coli.
    Science. 2007 Oct 26;318(5850):652-5 PMID: 17962566
  52. RASTA-Bacteria: a web-based tool for identifying toxin-antitoxin loci in prokaryotes.
    Genome Biol. 2007;8(8):R155 PMID: 17678530
  53. Selfish behavior of restriction-modification systems.
    Science. 1995 Feb 10;267(5199):897-9 PMID: 7846533
  54. Persister cells and the riddle of biofilm survival.
    Biochemistry (Mosc). 2005 Feb;70(2):267-74 PMID: 15807669
  55. Effects of the ccd function of the F plasmid on bacterial growth.
    J Bacteriol. 1985 Sep;163(3):841-9 PMID: 3897195
  56. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death.
    Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6059-63 PMID: 8650219
  57. pSM19035-encoded zeta toxin induces stasis followed by death in a subpopulation of cells.
    Microbiology (Reading). 2006 Aug;152(Pt 8):2365-2379 PMID: 16849801
  58. Persisters: a distinct physiological state of E. coli.
    BMC Microbiol. 2006 Jun 12;6:53 PMID: 16768798
  59. Bacterial programmed cell death and multicellular behavior in bacteria.
    PLoS Genet. 2006 Oct;2(10):e135 PMID: 17069462
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000437
Published
2009-03-00
Epub
2009-00-27
Pages
e1000437
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2654758
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pgen.1000437 PMC Full Text View journal details
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