title: The fimYZ genes regulate Salmonella enterica Serovar Typhimurium invasion in addition to type 1 fimbrial expression and bacterial motility.
abstract: An important step in Salmonella enterica serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme. A central player in the invasion regulatory pathway is the HilA protein, which is transcriptional activator belonging to the OmpR/ToxR family. A number of positive regulators (hilC, hilD, fis, sirA/barA, csrAB, phoBR, fadD, envZ/ompR, and fliZ) and negative regulators (hha, hilE, lon, ams, phoPc and pag) have been identified that are able to alter expression of hilA transcription. Recent work has found that hilA transcription requires the HilD protein for activation. Other work has emphasized the importance of HilE as a negative regulator of hilA. Overexpression of hilE superrepresses hilA transcription, as well as the invasive phenotype. Two-hybrid experiments suggest that HilE exerts its regulatory influence on hilA through protein-protein interactions with HilD as the protein does not bind to the hilA promoter nor does it affect hilD transcription. As it seems likely that hilE plays an important role in translating environmental signals into invasion gene regulation, we have attempted to identify how the hilE gene itself is regulated. Our results indicate that the fimYZ genes, response regulatory proteins involved in type 1 fimbrial gene expression and recently implicated in motility gene regulation, are important activators of hilE expression. These findings indicate that invasion gene expression is coregulated with motility and adherence and provide experimental evidence that the expression of these virulence phenotypes is a subset of the overall regulation of bacterial physiology.
authors.affiliation: Department of Microbiology, Roy J. and Lucille A. Carver School of Medicine, University of Iowa, Iowa City, IA 52242-1109. bradley-jones@uiowa.edu.
authors.forename: M Aaron
authors.initials: MA
authors.lastname: Baxter
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Jones
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009068:Movement; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; C102236:HilA protein, Salmonella; C119660:HilD protein, Salmonella typhimurium; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors
references.citation: J Bacteriol. 2000 Dec;182(23):6592-7
references.pmid: 11073900
references.citation: J Bacteriol. 1978 Jun;134(3):1141-56
references.pmid: 149110
references.citation: J Bacteriol. 1999 May;181(10):3096-104
references.pmid: 10322010
references.citation: J Bacteriol. 2002 Feb;184(4):1209-13
references.pmid: 11807085
references.citation: Mol Microbiol. 2002 Sep;45(5):1255-65
references.pmid: 12207694
references.citation: J Bacteriol. 2003 Sep;185(17):5096-108
references.pmid: 12923082
references.citation: J Biol Chem. 1997 Jan 17;272(3):1440-3
references.pmid: 8999810
references.citation: Mol Microbiol. 1995 Nov;18(4):715-27
references.pmid: 8817493
references.citation: Clin Microbiol Rev. 1999 Jul;12(3):405-28
references.pmid: 10398673
references.citation: FEMS Microbiol Lett. 1992 Aug 15;74(2-3):271-6
references.pmid: 1526459
references.citation: J Bacteriol. 1995 Dec;177(23):6861-5
references.pmid: 7592479
references.citation: Mol Microbiol. 2001 Jun;40(6):1289-99
references.pmid: 11442828
references.citation: Nature. 2001 Oct 25;413(6858):852-6
references.pmid: 11677609
references.citation: Gene. 1995 Oct 16;164(1):55-8
references.pmid: 7590321
references.citation: J Bacteriol. 2000 Apr;182(7):1872-82
references.pmid: 10714991
references.citation: Mol Microbiol. 2000 Feb;35(3):635-46
references.pmid: 10672185
references.citation: Mol Microbiol. 2003 Feb;47(3):715-28
references.pmid: 12535071
references.citation: Microbiol Rev. 1989 Dec;53(4):450-90
references.pmid: 2556636
references.citation: Annu Rev Microbiol. 1991;45:383-415
references.pmid: 1683764
references.citation: J Bacteriol. 2003 Jan;185(2):525-33
references.pmid: 12511499
references.citation: Mol Microbiol. 1996 Nov;22(4):703-14
references.pmid: 8951817
references.citation: Mol Microbiol. 1996 Nov;22(4):715-27
references.pmid: 8951818
references.citation: J Bacteriol. 2002 Jan;184(1):224-32
references.pmid: 11741864
references.citation: J Bacteriol. 1993 Jul;175(14):4475-84
references.pmid: 8392513
references.citation: Infect Immun. 2000 Jun;68(6):3305-13
references.pmid: 10816478
references.citation: Microbiol Immunol. 2002;46(1):1-10
references.pmid: 11911183
references.citation: Infect Immun. 1994 Sep;62(9):3745-52
references.pmid: 8063389
references.citation: FEMS Immunol Med Microbiol. 2000 May;28(1):25-35
references.pmid: 10767604
references.citation: J Bacteriol. 1987 Mar;169(3):934-8
references.pmid: 2880835
references.citation: Infect Immun. 2003 Mar;71(3):1295-305
references.pmid: 12595445
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references.pmid: 10829079
references.citation: Mol Microbiol. 1999 May;32(3):629-42
references.pmid: 10320584
references.citation: Biotechniques. 1995 Aug;19(2):186-8
references.pmid: 8527132
references.citation: Cancer Res. 1955 Oct;15(9):598-602
references.pmid: 13261081
references.citation: J Bacteriol. 1999 Sep;181(17):5516-20
references.pmid: 10464230
references.citation: Mol Microbiol. 2001 Jan;39(1):79-88
references.pmid: 11123690
references.citation: J Bacteriol. 1993 Apr;175(7):2026-36
references.pmid: 8458845
references.citation: Mol Microbiol. 1997 May;24(4):697-709
references.pmid: 9194698
references.citation: Infect Immun. 2000 Dec;68(12):6790-7
references.pmid: 11083797
references.citation: J Bacteriol. 2001 Mar;183(6):1835-42
references.pmid: 11222580
references.citation: J Bacteriol. 1992 Dec;174(23):7697-704
references.pmid: 1360005
references.citation: Mol Microbiol. 1997 May;24(4):747-56
references.pmid: 9194702
references.citation: Res Vet Sci. 1978 Sep;25(2):139-43
references.pmid: 364573
references.citation: Mol Microbiol. 1995 Jul;17(1):169-81
references.pmid: 7476203
references.citation: J Bacteriol. 2001 Nov;183(22):6620-9
references.pmid: 11673432
references.citation: J Bacteriol. 2002 Aug;184(15):4148-60
references.pmid: 12107132
references.citation: Methods. 2000 Jan;20(1):111-26
references.pmid: 10610809
references.citation: Proc Natl Acad Sci U S A. 1989 Jul;86(13):5054-8
references.pmid: 2544889
references.citation: Cell. 1986 Aug 15;46(4):551-5
references.pmid: 3524856
references.citation: Mol Microbiol. 1999 Jul;33(1):139-52
references.pmid: 10411731
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1847-51
references.pmid: 1311853