title: Contributions of the σ(W) , σ(M) and σ(X) regulons to the lantibiotic resistome of Bacillus subtilis.
abstract: In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σ(M) , σ(W) and σ(X) all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge-region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σ(M) to nisin resistance is expression of ltaSa, encoding a stress-activated lipoteichoic acid synthase, and σ(X) functions primarily by activation of the dlt operon controlling d-alanylation of teichoic acids. Together, σ(M) and σ(X) regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σ(W) is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σ(W) contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homologue) and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis.
authors: Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
authors: Anthony W
authors: AW
authors: Kingston
authors: Xiaojie
authors: X
authors: Liao
authors: John D
authors: JD
authors: Helmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D009561:Nisin / Q000378:metabolism* / Q000494:pharmacology; D009876:Operon; D012808:Sigma Factor / Q000378:metabolism*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012808:Sigma Factor; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D009561:Nisin
references: Antimicrob Agents Chemother. 2012 Nov;56(11):5749-57
references: 22926563
references: J Bacteriol. 2008 May;190(10):3475-81
references: 18326578
references: Appl Environ Microbiol. 2004 Mar;70(3):1669-79
references: 15006792
references: J Am Chem Soc. 2011 Mar 2;133(8):2338-41
references: 21114289
references: J Biol Chem. 1999 Mar 26;274(13):8405-10
references: 10085071
references: Mol Microbiol. 2011 Feb;79(3):566-83
references: 21255105
references: Nat Rev Microbiol. 2005 Oct;3(10):777-88
references: 16205711
references: Curr Pharm Biotechnol. 2009 Jan;10(1):2-18
references: 19149587
references: Science. 2006 Sep 15;313(5793):1636-7
references: 16973881
references: Nat Rev Microbiol. 2007 Mar;5(3):175-86
references: 17277795
references: Microbiology (Reading). 2005 May;151(Pt 5):1577-1592
references: 15870467
references: Mol Microbiol. 2006 May;60(3):765-82
references: 16629676
references: Annu Rev Microbiol. 2007;61:477-501
references: 17506681
references: J Bacteriol. 2010 Nov;192(21):5736-45
references: 20817771
references: Mol Microbiol. 2010 Oct;78(2):429-43
references: 20979344
references: Mol Microbiol. 2005 Aug;57(3):621-8
references: 16045608
references: Adv Microb Physiol. 2002;46:47-110
references: 12073657
references: PLoS One. 2012;7(11):e48471
references: 23155385
references: Mol Biol Evol. 2011 Mar;28(3):1141-55
references: 21059793
references: FEMS Microbiol Rev. 2011 Jan;35(1):201-32
references: 20695901
references: Mol Biosyst. 2012 Oct 30;8(12):3142-65
references: 23044854
references: J Innate Immun. 2009;1(2):70-87
references: 19756242
references: Microbiology (Reading). 2011 Jul;157(Pt 7):2033-2041
references: 21527469
references: J Mol Biol. 2004 Jul 16;340(4):783-95
references: 15223320
references: ACS Chem Biol. 2011 Jul 15;6(7):744-52
references: 21517116
references: J Bacteriol. 2006 Aug;188(16):5797-805
references: 16885447
references: Antimicrob Agents Chemother. 2009 May;53(5):1964-73
references: 19273681
references: J Biol Chem. 1995 Jun 30;270(26):15598-606
references: 7797557
references: J Bacteriol. 2004 Feb;186(4):1136-46
references: 14762009
references: Mol Microbiol. 2008 Feb;67(4):830-48
references: 18179421
references: J Bacteriol. 2010 Sep;192(18):4680-93
references: 20639339
references: Funct Integr Genomics. 2012 Mar;12(1):25-34
references: 21953179
references: J Biotechnol. 2009 Mar 10;140(1-2):27-37
references: 19041913
references: Mol Microbiol. 2012 Feb;83(3):623-39
references: 22211522
references: Curr Opin Pharmacol. 2012 Oct;12(5):545-50
references: 22776251
references: FEMS Microbiol Rev. 2008 Jan;32(1):107-46
references: 18173394
references: Nat Rev Microbiol. 2006 Jul;4(7):529-36
references: 16778838
references: J Biol Chem. 2003 Jan 3;278(1):89-94
references: 12379654
references: J Mol Biol. 2008 Feb 15;376(2):352-66
references: 18164727
references: Microbiol Mol Biol Rev. 2003 Dec;67(4):686-723
references: 14665680
references: Nucleic Acids Res. 2008 Apr;36(6):2032-46
references: 18276644
references: J Biol Chem. 1999 Aug 27;274(35):24585-92
references: 10455123
references: Mol Microbiol. 2003 Dec;50(5):1591-604
references: 14651641
references: Antimicrob Agents Chemother. 2010 Nov;54(11):4658-63
references: 20713661
references: Mol Microbiol. 2007 Apr;64(2):473-86
references: 17493129
references: Biochem Soc Trans. 2012 Dec 1;40(6):1528-33
references: 23176511
references: J Bacteriol. 2011 Nov;193(22):6223-32
references: 21926231
references: EMBO J. 2009 Apr 8;28(7):830-42
references: 19229300
references: Mol Microbiol. 2012 Aug;85(3):445-60
references: 22646656
references: J Leukoc Biol. 2005 Apr;77(4):466-75
references: 15582982
references: PLoS Pathog. 2012 Sep;8(9):e1002891
references: 22969424
references: J Bacteriol. 2010 Apr;192(7):1761-73
references: 20118250
references: Antimicrob Agents Chemother. 2004 Aug;48(8):2888-96
references: 15273097
references: Appl Environ Microbiol. 2009 Dec;75(23):7356-64
references: 19820159
references: Int J Med Microbiol. 2010 Feb;300(2-3):161-9
references: 20005776
references: Antimicrob Agents Chemother. 2008 Feb;52(2):612-8
references: 17999970
references: Microbiology (Reading). 2008 Jun;154(Pt 6):1755-1762
references: 18524930
references: J Food Prot. 1994 Oct;57(10):874-877
references: 31121693
references: Appl Environ Microbiol. 2009 Nov;75(21):6688-95
references: 19749059
references: Appl Environ Microbiol. 2001 Feb;67(2):808-13
references: 11157247
references: EMBO J. 2011 Sep 30;30(24):4931-41
references: 21964069
references: Chembiochem. 2010 Jan 4;11(1):35-45
references: 19899094
references: FEMS Microbiol Lett. 2011 Jun;319(2):97-105
references: 21388439
references: Nat Rev Microbiol. 2011 Jan;9(1):62-75
references: 21164535
references: J Mol Biol. 2002 Feb 22;316(3):443-57
references: 11866510
references: Mol Microbiol. 2008 Jul;69(1):218-30
references: 18485077
references: J Bacteriol. 2008 Apr;190(7):2633-6
references: 18223082
references: Nat Rev Microbiol. 2008 Apr;6(4):276-87
references: 18327271
references: Antimicrob Agents Chemother. 2011 Feb;55(2):515-25
references: 21078927
references: J Bacteriol. 2009 Aug;191(15):4951-8
references: 19465659
references: Antimicrob Agents Chemother. 2004 Dec;48(12):4673-9
references: 15561843
references: J Bacteriol. 2011 Jan;193(1):215-24
references: 20971906
references: Clin Infect Dis. 2009 Dec 1;49(11):1749-55
references: 19857164
references: Appl Environ Microbiol. 1999 Apr;65(4):1506-15
references: 10103244
references: Microbiology (Reading). 2013 Sep;159(Pt 9):1868-1877
references: 23858088
references: Microbiology (Reading). 2011 May;157(Pt 5):1457-1465
references: 21330441
references: Mol Microbiol. 2007 Oct;66(1):100-9
references: 17725563
references: J Mol Biol. 2012 Jun 22;419(5):347-58
references: 22472423
references: J Bacteriol. 2012 May;194(10):2594-605
references: 22389480
references: Nat Rev Drug Discov. 2006 Apr;5(4):321-32
references: 16531990
references: J Bacteriol. 2007 Oct;189(19):6919-27
references: 17675383
references: Antimicrob Agents Chemother. 2009 Apr;53(4):1598-609
references: 19164152
references: FEMS Microbiol Rev. 2010 Sep;34(5):797-827
references: 20636484
references: Peptides. 2001 Oct;22(10):1555-77
references: 11587785
references: PLoS One. 2012;7(10):e46884
references: 23056510