Structure, Evolution, and Functions of Bacterial Type III Toxin-Antitoxin Systems.
Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes. These TA systems were originally discovered through a phage resistance phenotype arising due to a process akin to an altruistic suicide; the phenomenon of abortive infection. Some Type III TA systems are bifunctional and can stabilise plasmids during vegetative growth and sporulation. Features particular to Type III systems are explored here, emphasising some of the characteristics of the RNA antitoxin and how these may affect the co-evolutionary relationship between toxins and cognate antitoxins in their quaternary structures. Finally, an updated analysis of the distribution and diversity of these systems are presented and discussed.
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. ng394@cam.ac.uk.
Nathalie
N
Goeders
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. rc636@cam.ac.uk.
Ray
R
Chai
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. bc407@cam.ac.uk.
Bihe
B
Chen
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. awd33@cam.ac.uk.
Andrew
A
Day
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. gpcs2@cam.ac.uk.
George P C
GP
Salmond
abortive infection; altruistic suicide; bacteriophages; co-evolution; endoribonuclease; pseudoknotted RNA; quaternary structures; type III toxin-antitoxin
Nat Rev Microbiol. 2010 May;8(5):317-27
20348932
Infect Immun. 2011 Jul;79(7):2502-9
21555398
Nucleic Acids Res. 2014 Apr;42(7):4590-605
24465005
Structure. 2002 Oct;10(10):1425-33
12377128
Nucleic Acids Res. 2015 Dec 2;43(21):10387-96
26553797
Cell Rep. 2015 Sep 1;12(9):1497-507
26299961
Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E241-9
23267117
Nat Chem Biol. 2012 Oct;8(10):855-61
22941047
Curr Opin Microbiol. 2005 Aug;8(4):473-9
15979388
J Bacteriol. 2013 Sep;195(17):3947-56
23813728
Appl Environ Microbiol. 2015 Jun;81(11):3848-55
25819963
Proc Natl Acad Sci U S A. 1986 May;83(10):3116-20
3517851
Toxins (Basel). 2014 Aug 04;6(8):2310-35
25093388
Nucleic Acids Res. 2015 Oct 30;43(19):9529-40
26350213
Nat Rev Microbiol. 2013 Oct;11(10):675-87
23979432
J Bacteriol. 2013 Jul;195(14):3165-72
23667234
Mol Biol Evol. 2016 Jun;33(6):1635-8
26921390
Mol Microbiol. 2016 Jan;99(1):188-98
26395283
Nat Microbiol. 2016 Apr 26;1:16056
27572651
Proc Natl Acad Sci U S A. 1983 Aug;80(15):4784-8
6308648
Syst Biol. 2003 Oct;52(5):696-704
14530136
J Bacteriol. 1996 Apr;178(7):2044-50
8606182
RNA Biol. 2015;12(9):933-7
26274022
J Mol Biol. 2001 Jun 29;310(1):243-57
11419950
Biochimie. 2015 Jul;114:10-7
25633441
FEMS Microbiol Lett. 2012 Mar;328(2):174-81
22239607
Curr Opin Microbiol. 2016 Apr;30:114-21
26874964
Nat Struct Mol Biol. 2011 Feb;18(2):185-90
21240270
Nat Biotechnol. 2004 Oct;22(10):1315-6
15470472
Plasmid. 2008 Sep;60(2):118-24
18582938
FEMS Microbiol Rev. 2014 Sep;38(5):916-31
24617569
PLoS Genet. 2012;8(10):e1003023
23109916
Biochem Biophys Res Commun. 2016 Apr 15;472(4):592-7
26972252
Appl Environ Microbiol. 1998 Dec;64(12):4748-56
9835558
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9
19124776
Mob Genet Elements. 2011 Nov 1;1(4):283-290
22545240
Mol Microbiol. 2013 Feb;87(4):756-68
23279123
J Mol Biol. 1999 Jan 29;285(4):1667-77
9917404
Nature. 2013 Jul 25;499(7459):431-7
23851394
J Bacteriol. 2009 Oct;191(19):6029-39
19633081
FEBS J. 2010 Aug;277(15):3097-117
20569269
FEMS Microbiol Rev. 2004 May;28(2):127-81
15109783
Acc Chem Res. 2011 Dec 20;44(12):1302-11
21899297
Nucleic Acids Res. 2012 Jul;40(13):6158-73
22434880
Nucleic Acids Res. 2011 Jul;39(13):5513-25
21422074
Biol Direct. 2009 Jun 03;4:19
19493340
Syst Biol. 2010 May;59(3):307-21
20525638
Nat Microbiol. 2016 Apr 11;1:16048
27572647
Mol Cell. 2003 Apr;11(4):875-84
12718874
Mol Genet Genomics. 2004 Sep;272(2):227-34
15316771
Toxins (Basel). 2014 Jan 10;6(1):304-24
24434905