Two AraC/XylS family members can independently counteract the effect of repressing sequences upstream of the hilA promoter

During infection of its hosts, Salmonella enterica serovar Typhimurium (S. typhimurium) enters the epithelial cells of the small intestine. This process requires a number of invasion genes encoded on Salmonella pathogenicity island 1 (SPI1), a 40 kb stretch of DNA located near minute 63 of the S. typhimurium chromosome. Expression of S. typhimurium SPI1 invasion genes is activated by the transcription factor HilA. hilA is tightly regulated in response to many environmental conditions, including oxygen, osmolarity and pH. Regulation of hilA expression may serve to limit invasion gene expression to the appropriate times during Salmonella infection. We have mapped the transcription start site of hilA and identified regions of the promoter that are required for the repression of hilA expression by conditions unfavourable for Salmonella invasion. We have also identified two SPI1‐encoded genes, hilC and hilD, that can independently derepress hilA expression. HilC and HilD are both members of the AraC/XylS family of transcriptional regulators. A mutation in hilD significantly reduces the ability of S. typhimurium to enter tissue culture cells, whereas a mutation in hilC only modestly affects Salmonella invasion. Based on these results, we have updated our model of Salmonella SPI1 invasion gene regulation. We also speculate on the possible significance of this model for Salmonella pathogenesis.

[1]  A. Takeuchi.  Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. , 1967, The American journal of pathology.

[2]  B. Stocker,et al.  Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines , 1981, Nature.

[3]  S. Falkow,et al.  The construction of a cloning vector designed for gene replacement in Bordetella pertussis. , 1986, Gene.

[4]  B. Washburn,et al.  New method for generating deletions and gene replacements in Escherichia coli , 1989, Journal of bacteriology.

[5]  J. Galán,et al.  Expression of Salmonella typhimurium genes required for invasion is regulated by changes in DNA supercoiling , 1990, Infection and immunity.

[6]  S. Falkow,et al.  The ability of Salmonella to enter mammalian cells is affected by bacterial growth state. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Xunzhang Wang,et al.  Baculovirus vectors for multiple gene expression and for occluded virus production. , 1991, Gene.

[8]  T. Michiels,et al.  ymoA, a Yersinia enterocolitica chromosomal gene modulating the expression of virulence functions , 1991, Molecular microbiology.

[9]  S. Bolland,et al.  The hha gene modulates haemolysin expression in Escherichia coli , 1991, Molecular microbiology.

[10]  R. F. Wang,et al.  Construction of versatile low-copy-number vectors for cloning, sequencing and gene expression in Escherichia coli. , 1991, Gene.

[11]  Jeffrey H. Miller,et al.  A short course in bacterial genetics , 1992 .

[12]  B. Uhlin,et al.  The positive regulator CfaD overcomes the repression mediated by histone‐like protein H‐NS (H1) in the CFA/I fimbrial operon of Escherichia coli. , 1992, The EMBO journal.

[13]  N. R. Kamini,et al.  Broad host range plasmids carrying the Escherichia coli lactose and galactose operons. , 1992, FEMS microbiology letters.

[14]  S. Falkow,et al.  Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Cornelis,et al.  Role of the transcriptional activator, VirF, and temperature in the expression of the pYV plasmid genes of Yersinia enterocolitica. , 1992, Molecular microbiology.

[16]  O. Kapp,et al.  Electron microscope studies , 1992 .

[17]  S. Falkow,et al.  Invasion by Salmonella typhimurium is affected by the direction of flagellar rotation , 1992, Infection and immunity.

[18]  C. Sasakawa,et al.  Transcriptional control of the invasion regulatory gene virB of Shigella flexneri: activation by virF and repression by H-NS , 1993, Journal of bacteriology.

[19]  Roberto Spurio,et al.  Expression of the gene encoding the major bacterial nucleoid protein H‐NS is subject to transcriptional auto‐repression , 1993, Molecular microbiology.

[20]  E. Metcalf,et al.  Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells , 1993, Infection and immunity.

[21]  F. Cruz,et al.  Escherichia coli hha mutants, DNA supercoiling and expression of the haemolysin genes from the recombinant plasmid pANN202‐312 , 1993, Molecular microbiology.

[22]  S. Miller,et al.  A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells , 1993, Journal of bacteriology.

[23]  J. Galán,et al.  The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins , 1994, Molecular microbiology.

[24]  D. Ussery,et al.  The chromatin‐associated protein H‐NS alters DNA topology in vitro. , 1994, The EMBO journal.

[25]  D. K. Willis,et al.  Genetic evidence that the gacA gene encodes the cognate response regulator for the lemA sensor in Pseudomonas syringae , 1994, Journal of bacteriology.

[26]  S. Miller,et al.  Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis , 1995, Infection and immunity.

[27]  D. Schiemann.  Association with MDCK epithelial cells by Salmonella typhimurium is reduced during utilization of carbohydrates , 1995, Infection and immunity.

[28]  S. Miller,et al.  PhoP/PhoQ transcriptional repression of Salmonella typhimurium invasion genes: evidence for a role in protein secretion , 1995, Molecular microbiology.

[29]  Regulation of Capsule Synthesis: Modification of the Two-Component Paradigm by an Accessory Unstable Regulator , 1995 .

[30]  S. Falkow,et al.  Entry of microbes into the host: using M cells to break the mucosal barrier. , 1995, Current opinion in immunology.

[31]  S. Miller,et al.  Salmonella typhimurium secreted invasion determinants are homologous to Shigella lpa proteins , 1995, Molecular microbiology.

[32]  Catherine A. Lee,et al.  A 40 kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K‐12 chromosome , 1995, Molecular microbiology.

[33]  Catherine A. Lee,et al.  hilA is a novel ompR/toxR family member that activates the expression of Salmonella typhimurium invasion genes , 1995, Molecular microbiology.

[34]  J. Bliska,et al.  A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurlum , 1996, Molecular microbiology.

[35]  S. Miller,et al.  Transcriptional regulation of Salmonella virulence: a PhoQ periplasmic domain mutation results in increased net phosphotransfer to PhoP , 1996, Journal of bacteriology.

[36]  Samuel I. Miller,et al.  Transcriptional activation of Salmonella typhimurium invasion genes by a member of the phosphorylated response‐regulator superfamily , 1996, Molecular microbiology.

[37]  R. L. Lucas,et al.  Co‐ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression , 1996, Molecular microbiology.

[38]  E. Groisman,et al.  Mg2+ as an Extracellular Signal: Environmental Regulation of Salmonella Virulence , 1996, Cell.

[39]  S. Falkow,et al.  Salmonella typhimurium invasion induces apoptosis in infected macrophages. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Mullan,et al.  SopE, a secreted protein of Salmonelladublin, is translocated into the target eukaryotic cell via a sip‐dependent mechanism and promotes bacterial entry , 1996, Molecular microbiology.

[41]  J. O. Lee,et al.  Characterization of the rcsA and rcsB genes from Salmonella typhi: rcsB through tviA is involved in regulation of Vi antigen synthesis , 1996, Journal of bacteriology.

[42]  H. Ochman,et al.  Identification of a pathogenicity island required for Salmonella survival in host cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  J. Galán,et al.  Salmonella spp. are cytotoxic for cultured macrophages , 1996, Molecular microbiology.

[44]  A. Lupas.  Prediction and analysis of coiled-coil structures. , 1996, Methods in enzymology.

[45]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[46]  C. Lee,et al.  Type III secretion systems: machines to deliver bacterial proteins into eukaryotic cells? , 1997, Trends in microbiology.

[47]  H. Ingmer,et al.  H‐NS: a modulator of environmentally regulated gene expression , 1997, Molecular microbiology.

[48]  Arac/XylS family of transcriptional regulators. , 1997, Microbiology and molecular biology reviews : MMBR.

[49]  S. Levy,et al.  Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon , 1997, Antimicrobial agents and chemotherapy.

[50]  C. Wolberger,et al.  Structural basis for ligand-regulated oligomerization of AraC. , 1997, Science.

[51]  V. DiRita,et al.  Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae , 1997, Molecular microbiology.

[52]  S Falkow,et al.  Copyright © 1997, American Society for Microbiology Common Themes in Microbial Pathogenicity Revisited , 2022 .

[53]  J. Galán,et al.  The invasion-associated type-III protein secretion system in Salmonella--a review. , 1997, Gene.

[54]  G. Church,et al.  Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterization , 1997, Journal of bacteriology.

[55]  R. Taylor,et al.  Control of the ToxR virulence regulon in Vibrio cholerae by environmental stimuli , 1997, Molecular microbiology.

[56]  W. Hardt,et al.  A secreted Salmonella protein with homology to an avirulence determinant of plant pathogenic bacteria. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. Shea,et al.  Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages , 1998, Molecular microbiology.

[58]  S Falkow,et al.  Macrophage‐dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival , 1998, Molecular microbiology.

[59]  J. Galán,et al.  The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton , 1998, Molecular microbiology.

[60]  K. Schuebel,et al.  S. typhimurium Encodes an Activator of Rho GTPases that Induces Membrane Ruffling and Nuclear Responses in Host Cells , 1998, Cell.

[61]  M. Hensel,et al.  Mutations in Salmonella Pathogenicity Island 2 (SPI2) Genes Affecting Transcription of SPI1 Genes and Resistance to Antimicrobial Agents , 1998, Journal of bacteriology.

[62]  E. Groisman.  The ins and outs of virulence gene expression: Mg2+ as a regulatory signal. , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[63]  J. Mekalanos,et al.  TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[64]  C. Hueck,et al.  Type III Protein Secretion Systems in Bacterial Pathogens of Animals and Plants , 1998, Microbiology and Molecular Biology Reviews.

[65]  M. Popoff,et al.  The RcsB–RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity , 1998, Molecular microbiology.

[66]  J. van Reeuwijk,et al.  Salmonella SirA is a global regulator of genes mediating enteropathogenesis , 1999, Molecular Microbiology.