Disease relevance of hilA

• HilE interacts with HilD and negatively regulates hilA transcription and expression of the Salmonella enterica serovar Typhimurium invasive phenotype [1].
• We have reconstituted HilA-dependent activation of both promoters in Escherichia coli by supplying hilA on a plasmid, strongly suggesting that HilA acts directly on the promoters [2].
• Both sirA and hilA mutants are dramatically attenuated in a bovine model of gastroenteritis, but have little or no effect in the mouse model of typhoid fever [3].

High impact information on hilA

• We demonstrate that HilC, HilD and RtsA are each capable of independently inducing expression of the hilC, hilD and rtsA genes, and that each can independently activate hilA [4].
• The two-component regulatory systems, SirA/BarA and OmpR/EnvZ, function through HilD, thus inducing hilC, rtsA and hilA [4].
• The DeltarelADeltaspoT strain exhibited severely reduced expression of hilA and invF, encoding major transcriptional activators required for Salmonella pathogenicity island 1 (SPI-1) gene expression and at least two other pathogenicity islands [5].
• This repression requires an upstream repressing sequence (URS) located between -314 and -68 relative to the hilA transcription start site [6].
• HilA, a member of the OmpR/ToxR family of transcriptional regulators, directly activates the expression of two SPI1 operons encoding type III apparatus components. hilA transcription is repressed by many environmental conditions and regulatory mutations [6].

Chemical compound and disease context of hilA

• Mechanism of hilA repression by 1,2-propanediol consists of two distinct pathways, one dependent on and the other independent of catabolic production of propionate, in Salmonella enterica serovar Typhimurium [7].
• Expression of the hilA Salmonella typhimurium gene in a poultry Salm. enteritidis isolate in response to lactate and nutrients [8].

Biological context of hilA

• We have characterized the Salmonella-specific gene, hilE, and found that it plays an important regulatory role in hilA transcription and invasion gene expression [1].
• Recent work indicates that the small DNA-binding protein, Hha, has a significant role in repressing hilA transcription and the invasive phenotype, particularly in response to osmolarity signals [1].
• The majority of the genes responsible for the Salmonella invasive phenotype are encoded on Salmonella pathogenicity island 1, and their transcription is controlled by the hilA transcriptional activator [9].
• Expression of the minimal hilA core promoter (-55 to +90, relative to the transcription start site) was 57-times higher than the intact promoter (-242 to +505) in the absence of osmotic stress [10].
• Action of activators requires contact with RNA polymerase from their DNA binding site, centered at position -77, relative to the hilA transcription start site [10].

Anatomical context of hilA

• Our results indicate that Lon protease is important for down-regulation of hilA expression and intracellular survival after the invasion of epithelial cells [11].
• Transcription of the hilA gene, which encodes an OmpR/ToxR-type transcriptional activator of downstream invasion genes, is increased during growth under high-osmolarity and low-oxygen conditions, which presumably mimic the environment found within the small intestine [11].
• Expression of hilA, a central regulator of SPI1 transcription, was repressed in the macrophages after phagocytosis, but this gene was continuously expressed when the DeltaLon mutant grew within the macrophages, so the SPI1 proteins accumulated [12].
• We have found that strains containing a mutation in hilA or invG were recovered from the intestinal contents, intestinal tissues, and systemic tissues at a lower frequency than their parental wild-type strain [13].
• Thus, fatty acid derivatives may act as intracellular signals to regulate hilA expression. flhDC and fliA encode transcription factors required for flagellum production, motility, and chemotaxis [14].

Associations of hilA with chemical compounds

• A substrate of the enzyme, 1,2-propanediol, repressed hilA expression [7].
• Lactate (25 and 50 mmmol 1-1) reduced hilA expression at pH 6, 5 and 4, with the lowest expression occurring at pH 4 [8].
• Addition of 0.2% Casaminoacids, arabinose, fucose, or lactose had little effect on hilA expression [8].
• Addition of 0.2% glucose, fructose or mannose to LB and DLB reduced hilA expression 1.5 to twofold [8].

Regulatory relationships of hilA

• Modulation of hilA by counteracting repressing and derepressing mechanisms may allow Salmonella serovar Typhimurium to regulate its virulence genes in response to different situations in vivo [15].

Other interactions of hilA

• Identification and characterization of mutants with increased expression of hilA, the invasion gene transcriptional activator of Salmonella typhimurium [16].
• The hilA and hilC promoters contain multiple binding sites of each type, whereas the hilD promoter contains a site that binds HilC but not HilD without additional binding elements [17].
• The HilC and HilD proteins had no major effect on transcription from the hilA or hilD promoters using purified proteins in vitro but changed the choice of promoter at hilC [17].
• A glycerol dehydrogenase gene was selected as a multicopy suppressor rescuing the reduced hilA expression in the Salmonella enterica serovar Typhimurium cpxA mutant [7].
• SirA of Salmonella typhimurium is known to regulate the hilA and prgH genes within Salmonella pathogenicity island 1 (SPI1) [3].

Analytical, diagnostic and therapeutic context of hilA

• Simple and rapid detection of Salmonella strains by direct PCR amplification of the hilA gene [18].

References