title: Rat/MgrA, a regulator of autolysis, is a regulator of virulence genes in Staphylococcus aureus.
abstract: We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of alpha-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and vice versa, indicating that MgrA likely regulates hla and spa in a SarA-independent manner. Previously we have shown that SarT, a SarA homolog, is a repressor of hla and an activator of spa, presumably by activating SarS, however, analysis of the double sarT mgrA mutant for hla and spa transcription indicated that the mgrA-mediated effect is not mediated via sarT. Our results further demonstrated that the mgrA gene product regulates hla and spa expression in a dual fashion, with the first being agr dependent and the second agr independent. In the agr-independent pathway, MgrA binds directly to hla and the sarS promoter to modulate alpha-hemolysin and protein A expression. Thus, our studies here have defined the nature of interaction of mgrA with other regulators such as agr, sarS, and sarT and its role in regulating hla and spa transcription within the virulence regulatory network of S. aureus.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Susham
authors.initials: S
authors.lastname: Ingavale
authors.forename: Willem
authors.initials: W
authors.lastname: van Wamel
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001433:Bacteriolysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D006460:Hemolysin Proteins; D012097:Repressor Proteins; C433204:SarH3 protein, Staphylococcus aureus; C476149:SarS protein, Staphylococcus aureus; D013205:Staphylococcal Protein A; D015534:Trans-Activators; D037521:Virulence Factors
references.citation: Infect Immun. 2003 Jan;71(1):343-53
references.pmid: 12496184
references.citation: J Biol Chem. 1998 Jan 30;273(5):2645-52
references.pmid: 9446568
references.citation: N Engl J Med. 1998 Aug 20;339(8):520-32
references.pmid: 9709046
references.citation: Front Biosci. 2002 Aug 01;7:d1825-42
references.pmid: 12133812
references.citation: J Bacteriol. 2004 Apr;186(8):2430-8
references.pmid: 15060046
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12055-9
references.pmid: 8618843
references.citation: J Bacteriol. 2004 Aug;186(16):5267-80
references.pmid: 15292128
references.citation: J Immunol. 2003 Nov 15;171(10):5389-95
references.pmid: 14607942
references.citation: Infect Immun. 2001 Feb;69(2):885-96
references.pmid: 11159982
references.citation: N Engl J Med. 2003 Apr 3;348(14):1342-7
references.pmid: 12672861
references.citation: J Antimicrob Chemother. 1997 Jul;40(1):135-6
references.pmid: 9249217
references.citation: Mol Microbiol. 2003 Jun;48(6):1429-49
references.pmid: 12791129
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6462-6
references.pmid: 1321441
references.citation: Mol Microbiol. 2000 Jul;37(2):398-409
references.pmid: 10931334
references.citation: Infect Immun. 2001 Dec;69(12):7858-65
references.pmid: 11705968
references.citation: Mol Microbiol. 2003 Aug;49(3):807-21
references.pmid: 12864861
references.citation: Microbiology (Reading). 2003 Oct;149(Pt 10):2709-2717
references.pmid: 14523104
references.citation: Mol Microbiol. 2001 Jul;41(1):247-61
references.pmid: 11454217
references.citation: FEMS Microbiol Lett. 1992 Jul 1;73(1-2):133-8
references.pmid: 1521761
references.citation: FEMS Immunol Med Microbiol. 2004 Jan 15;40(1):1-9
references.pmid: 14734180
references.citation: J Bacteriol. 2001 Feb;183(4):1113-23
references.pmid: 11157922
references.citation: J Bacteriol. 1996 Aug;178(15):4563-70
references.pmid: 8755885
references.citation: J Bacteriol. 2001 Dec;183(24):7341-53
references.pmid: 11717293
references.citation: J Bacteriol. 1996 Oct;178(20):6036-42
references.pmid: 8830703
references.citation: Mol Microbiol. 2003 Jun;48(6):1451-66
references.pmid: 12791130
references.citation: J Bacteriol. 1994 Feb;176(3):580-5
references.pmid: 7507919
references.citation: J Bacteriol. 1994 Jul;176(13):4168-72
references.pmid: 8021198
references.citation: Infect Immun. 2001 Apr;69(4):2448-55
references.pmid: 11254606
references.citation: Mol Gen Genet. 1995 Aug 30;248(4):446-58
references.pmid: 7565609
references.citation: J Biol Chem. 1999 Dec 24;274(52):37169-76
references.pmid: 10601279
references.citation: Arch Microbiol. 1997 Jul;168(1):53-8
references.pmid: 9211714
references.citation: Infect Immun. 2000 Sep;68(9):5385-92
references.pmid: 10948168
references.citation: Int J Med Microbiol. 2001 May;291(2):159-70
references.pmid: 11437338
references.citation: MMWR Morb Mortal Wkly Rep. 2002 Jul 5;51(26):565-7
references.pmid: 12139181
references.citation: J Bacteriol. 2003 May;185(10):3127-38
references.pmid: 12730173
references.citation: FEMS Microbiol Lett. 1999 Aug 1;177(1):15-22
references.pmid: 10436918
references.citation: J Bacteriol. 1996 Feb;178(3):611-8
references.pmid: 8550490
references.citation: Infect Immun. 2003 Sep;71(9):5139-48
references.pmid: 12933857
references.citation: J Bacteriol. 1999 Jun;181(12):3666-73
references.pmid: 10368139
references.citation: J Bacteriol. 2003 Jul;185(13):3703-10
references.pmid: 12813062
references.citation: Anal Biochem. 1994 Nov 1;222(2):511-4
references.pmid: 7532381
references.citation: J Clin Invest. 2003 Jul;112(2):222-33
references.pmid: 12865410
references.citation: EMBO J. 1990 May;9(5):1391-9
references.pmid: 2328718
references.citation: Curr Microbiol. 2003 Apr;46(4):246-50
references.pmid: 12732971
references.citation: Infect Immun. 2001 Aug;69(8):4749-58
references.pmid: 11447147
references.citation: J Bacteriol. 1997 Jun;179(12):3963-71
references.pmid: 9190813
references.citation: EMBO J. 1993 Oct;12(10):3967-75
references.pmid: 7691599
references.citation: Mol Microbiol. 1994 Jan;11(2):237-48
references.pmid: 8170386
references.citation: J Bacteriol. 2003 Nov;185(21):6278-86
references.pmid: 14563862
references.citation: Science. 1997 Jun 27;276(5321):2027-30
references.pmid: 9197262