title: sRNA antitoxins: more than one way to repress a toxin.
abstract: Bacterial toxin-antitoxin loci consist of two genes: one encodes a potentially toxic protein, and the second, an antitoxin to repress its function or expression. The antitoxin can either be an RNA or a protein. For type I and type III loci, the antitoxins are RNAs; however, they have very different modes of action. Type I antitoxins repress toxin protein expression through interacting with the toxin mRNA, thereby targeting the mRNA for degradation or preventing its translation or both; type III antitoxins directly bind to the toxin protein, sequestering it. Along with these two very different modes of action for the antitoxin, there are differences in the functions of the toxin proteins and the mobility of these loci between species. Within this review, we discuss the major differences as to how the RNAs repress toxin activity, the potential consequences for utilizing different regulatory strategies, as well as the confirmed and potential biological roles for these loci across bacterial species.
authors.affiliation: Department of Microbiology, University of Tennessee, M409 Walters Life Sciences, Knoxville, TN 37996, USA. jwen@vols.utk.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Microbiology, University of Tennessee, M409 Walters Life Sciences, Knoxville, TN 37996, USA. efozo@utk.edu.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Fozo
mesh_terms: D000992:Antitoxins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D012329:RNA, Bacterial
references.citation: Clin Infect Dis. 2001 Mar 15;32 Suppl 1:S9-S15
references.pmid: 11249823
references.citation: Nucleic Acids Res. 2012 Jul;40(13):6158-73
references.pmid: 22434880
references.citation: J Mol Biol. 1992 Jan 5;223(1):41-54
references.pmid: 1370544
references.citation: RNA Biol. 2012 Dec;9(12):1513-9
references.pmid: 23093802
references.citation: Mol Microbiol. 2002 Jul;45(2):333-49
references.pmid: 12123448
references.citation: J Bacteriol. 1996 Apr;178(7):2044-50
references.pmid: 8606182
references.citation: Mol Microbiol. 1991 Aug;5(8):1961-73
references.pmid: 1722558
references.citation: Mol Microbiol. 2013 Feb;87(4):756-68
references.pmid: 23279123
references.citation: RNA Biol. 2012 Dec;9(12):1498-503
references.pmid: 23059908
references.citation: Curr Opin Microbiol. 2007 Apr;10(2):110-6
references.pmid: 17376732
references.citation: Curr Opin Microbiol. 2007 Apr;10(2):117-24
references.pmid: 17376733
references.citation: Sci Rep. 2013 Nov 11;3:3186
references.pmid: 24212724
references.citation: Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):742-7
references.pmid: 23500183
references.citation: J Biol Chem. 2012 Dec 21;287(52):43454-63
references.pmid: 23129767
references.citation: Nucleic Acids Res. 2014 Feb;42(3):1930-46
references.pmid: 24203704
references.citation: Nucleic Acids Res. 2011 Jul;39(13):5513-25
references.pmid: 21422074
references.citation: Mol Microbiol. 1996 Sep;21(5):1049-60
references.pmid: 8885274
references.citation: J Bacteriol. 2004 Oct;186(19):6400-8
references.pmid: 15375120
references.citation: RNA Biol. 2012 Dec;9(12):1520-7
references.pmid: 23131729
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9
references.pmid: 19124776
references.citation: Nat Rev Microbiol. 2013 Oct;11(10):675-87
references.pmid: 23979432
references.citation: Nat Rev Microbiol. 2007 Jan;5(1):48-56
references.pmid: 17143318
references.citation: Microbiology (Reading). 2009 Sep;155(Pt 9):2930-2940
references.pmid: 19542006
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12541-6
references.pmid: 20616060
references.citation: Environ Microbiol. 2010 May;12(5):1105-21
references.pmid: 20105222
references.citation: Genes Dev. 1990 Apr;4(4):525-35
references.pmid: 2163341
references.citation: Microbiol Mol Biol Rev. 2008 Dec;72(4):579-89, Table of Contents
references.pmid: 19052321
references.citation: Curr Biol. 2001 Jun 26;11(12):941-50
references.pmid: 11448770
references.citation: PLoS Genet. 2013;9(2):e1003260
references.pmid: 23408903
references.citation: J Bacteriol. 1977 Dec;132(3):784-9
references.pmid: 336605
references.citation: Mol Microbiol. 2008 Oct;70(1):258-70
references.pmid: 18761622
references.citation: Mol Microbiol. 2000 Aug;37(3):652-60
references.pmid: 10931358
references.citation: J Bacteriol. 2001 Dec;183(24):7371-80
references.pmid: 11717296
references.citation: DNA Res. 2002 Feb 28;9(1):1-10
references.pmid: 11939563
references.citation: FEMS Microbiol Rev. 2009 Jul;33(4):704-17
references.pmid: 19207742
references.citation: Gene. 1988 Jun 30;66(2):259-68
references.pmid: 3049248
references.citation: J Bacteriol. 2003 Apr;185(7):2169-77
references.pmid: 12644486
references.citation: J Bacteriol. 1980 Nov;144(2):833-5
references.pmid: 6159347
references.citation: Infect Immun. 2014 Sep;82(9):3599-611
references.pmid: 24914223
references.citation: Science. 1975 Jan 24;187(4173):257-8
references.pmid: 1089310
references.citation: Nucleic Acids Res. 2013 Nov;41(21):9870-80
references.pmid: 23969414
references.citation: Mol Microbiol. 2012 Apr;84(1):17-35
references.pmid: 22289118
references.citation: Mol Microbiol. 2001 Oct;42(2):527-37
references.pmid: 11703673
references.citation: Mol Microbiol. 1996 Apr;20(1):53-63
references.pmid: 8861204
references.citation: Environ Microbiol. 2012 Mar;14(3):669-79
references.pmid: 22026739
references.citation: PLoS Biol. 2010 Feb 23;8(2):e1000317
references.pmid: 20186264
references.citation: Mol Microbiol. 2000 Aug;37(3):661-70
references.pmid: 10931359
references.citation: Nat Struct Mol Biol. 2011 Feb;18(2):185-90
references.pmid: 21240270
references.citation: J Bacteriol. 2004 Jun;186(12):3677-86
references.pmid: 15175280
references.citation: Virology. 2007 Sep 1;365(2):241-9
references.pmid: 17482656
references.citation: Dev Biol Stand. 1995;85:89-98
references.pmid: 8586250
references.citation: Nat Struct Mol Biol. 2011 Dec 25;19(1):105-12
references.pmid: 22198463
references.citation: EMBO J. 1986 Aug;5(8):2023-9
references.pmid: 3019679
references.citation: Acta Biochim Pol. 2001;48(4):1003-23
references.pmid: 11995964
references.citation: Cell Rep. 2014 Apr 24;7(2):424-435
references.pmid: 24703849
references.citation: Res Microbiol. 1999 Nov-Dec;150(9-10):653-64
references.pmid: 10673004
references.citation: J Bacteriol. 2006 Aug;188(15):5374-84
references.pmid: 16855226
references.citation: Plasmid. 1994 Sep;32(2):168-81
references.pmid: 7531349
references.citation: J Bacteriol. 1995 Jul;177(14):4194-7
references.pmid: 7608103
references.citation: J Mol Biol. 1997 Oct 17;273(1):38-51
references.pmid: 9367744
references.citation: J Bacteriol. 1998 Apr;180(7):1655-61
references.pmid: 9537360
references.citation: J Bacteriol. 2011 Nov;193(21):6039-56
references.pmid: 21908672
references.citation: Curr Biol. 2004 Dec 29;14(24):2271-6
references.pmid: 15620655
references.citation: Nucleic Acids Res. 2010 Oct;38(19):6637-51
references.pmid: 20525796
references.citation: J Mol Biol. 1992 Aug 5;226(3):637-49
references.pmid: 1380562
references.citation: RNA Biol. 2013 Apr;10(4):619-26
references.pmid: 23466677
references.citation: J Bacteriol. 2005 Oct;187(19):6641-50
references.pmid: 16166525
references.citation: J Biotechnol. 2003 Jan 9;100(1):1-12
references.pmid: 12413781
references.citation: Mol Microbiol. 1999 Jun;32(5):1090-102
references.pmid: 10361310
references.citation: J Bacteriol. 2014 Feb;196(3):693-706
references.pmid: 24272782
references.citation: PLoS Genet. 2012;8(12):e1003181
references.pmid: 23300471
references.citation: Microb Biotechnol. 2010 Nov;3(6):634-57
references.pmid: 21255361
references.citation: Mol Cell. 2007 May 11;26(3):381-92
references.pmid: 17499044
references.citation: Mol Microbiol. 2008 Dec;70(5):1076-93
references.pmid: 18710431
references.citation: Nucleic Acids Res. 2010 Jun;38(11):3743-59
references.pmid: 20156992
references.citation: Microbiol Immunol. 1982;26(9):779-93
references.pmid: 6185827
references.citation: J Bacteriol. 1991 Aug;173(15):4827-35
references.pmid: 1906873
references.citation: Phys Biol. 2010 Dec 09;7(4):045002
references.pmid: 21149972
references.citation: Cell. 2011 Jan 7;144(1):143-56
references.pmid: 21185072
references.citation: PLoS One. 2013;8(1):e54291
references.pmid: 23326602
references.citation: Nucleic Acids Res. 2005 Feb 17;33(3):966-76
references.pmid: 15718296
references.citation: Antimicrob Agents Chemother. 2013 Mar;57(3):1468-73
references.pmid: 23295927
references.citation: Mol Microbiol. 2007 May;64(3):738-54
references.pmid: 17462020
references.citation: Toxins (Basel). 2014 Jan 10;6(1):304-24
references.pmid: 24434905
references.citation: Biophys J. 2012 Oct 3;103(7):1460-9
references.pmid: 23062338
references.citation: RNA Biol. 2012 Dec;9(12):1491-7
references.pmid: 23059907
references.citation: Biochim Biophys Acta. 1983 Jan 20;739(1):27-34
references.pmid: 6187365
references.citation: Nat Chem Biol. 2011 Jun;7(6):359-66
references.pmid: 21516113
references.citation: Mol Microbiol. 2000 Mar;35(6):1560-72
references.pmid: 10760155
references.citation: Genes Dev. 2013 May 15;27(10):1132-45
references.pmid: 23666921
references.citation: J Biol Chem. 2001 Sep 21;276(38):35707-13
references.pmid: 11461923
references.citation: Biol Direct. 2009 Jun 03;4:19
references.pmid: 19493340
references.citation: Gene. 2009 Jan 1;428(1-2):2-8
references.pmid: 18948176
references.citation: J Mol Microbiol Biotechnol. 2013;23(6):440-7
references.pmid: 24089053
references.citation: Mol Microbiol. 1990 Nov;4(11):1807-18
references.pmid: 1707122
references.citation: Nucleic Acids Res. 2010 Sep;38(17):5851-66
references.pmid: 20453032
references.citation: FEBS Lett. 2012 Jul 30;586(16):2529-34
references.pmid: 22728134
references.citation: Virology. 1983 Apr 15;126(1):168-82
references.pmid: 6221468
references.citation: Nucleic Acids Res. 2014 Jun;42(10):6448-62
references.pmid: 24748661
references.citation: Mol Microbiol. 2012 Feb;83(3):579-98
references.pmid: 22229825
references.citation: Appl Environ Microbiol. 1998 Dec;64(12):4748-56
references.pmid: 9835558
references.citation: New Biol. 1990 Nov;2(11):946-56
references.pmid: 2101633
references.citation: Curr Top Microbiol Immunol. 2008;322:107-31
references.pmid: 18453274
references.citation: PLoS Genet. 2009 Dec;5(12):e1000760
references.pmid: 20011100
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13206-11
references.pmid: 21788497
references.citation: J Bacteriol. 2013 Jan;195(1):156-66
references.pmid: 23104812