Genetic evidence for histidine kinase HP165 being an acid sensor of Helicobacter pylori

Abstract

Helicobacter pylori is a human gastric pathogen which is extremely well adapted to its unique habitat. Crucial for the survival under the acidic conditions prevailing in the stomach is the enzyme urease. Transcriptome analysis has shown that transcription of a large number of genes responds to the exposure of H. pylori to acid including the genes encoding the urease subunits UreA and UreB as well as several genes which have been previously identified as target genes of the two-component system HP166-HP165. Here, we provide genetic evidence that a stimulus perceived by the histidine kinase HP165 is pH since increased transcription at acidic pH from the promoters controlling the expression of the ORFs hp119 and hp1432 which belong to the HP166-HP165 regulon is strictly dependent on the presence of histidine kinase HP165. Furthermore, we show that the basal transcription from the promoter of the ureA gene is modulated by the HP166-HP165 two-component system in response to acidic pH. On the other hand, the acid-induced increase in transcription of the promoter directing the expression of the orphan response regulator HP1021 is not controlled by the HP166-HP165 two-component system, nor is it mediated by HP1021 itself.

Nickel-binding and accessory proteins facilitating Ni-enzyme maturation in Helicobacter pylori

“…Hpn-like is upregulated at pH 5.0 (compared to pH 7.0) by the two-component system ArsRS (HP166-HP165) (Bury-Mone et al 2004;Pflock et al 2004;Pflock et al 2006). Both Hpn and Hpn-like are activated in the presence of nickel by the nickel sensor NikR (Contreras et al 2003).The regulation studies thus far suggest that the Hpn proteins would be expressed at a time when nickel detoxification and/or nickel storage would be an advantage.…”

Novel Insights into Fur Regulation in Helicobacter pylori

“…ArsR has been shown to regulate expression of numerous genes and appears to have the ability to interact with the promoters of some genes in the non-phosphorylated form while interacting with others only when phosphorylated (126,127,171). Previous EMSA assays showed that ArsR directly binds to the oorDABC promoter region and that this reaction did not require ArsR phosphorylation (171).…”

Structural Analysis of the DNA-binding Domain of the Helicobacter pylori Response Regulator ArsR

“…Therefore, H. pylori has evolved mechanisms to survive severe acid shock and grow under moderately acidic conditions. One of the important mechanisms by which H. pylori responds to acidic pH involves regulation of gene expression through a two-component signal transduction system (12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Several recent studies reported that an H. pylori TCS, ArsSArsR (acid-responsive signaling sensor/response regulator), responds to acidic conditions (12)(13)(14)(15)(16)(17)(18)(19)(20). This TCS consists of the histidine kinase protein, ArsS, and the RR protein, ArsR.…”

“…It has been proposed that the periplasmic domain of ArsS detects low pH conditions (16,27), triggering an ATP-dependent autophosphorylation reaction at a conserved histidine residue in the protein cytoplasmic domain. This model proposes that the signal from ArsS is then transduced to the cognate RR protein, ArsR, via a phosphotransfer reaction from the phosphohistidine kinase to a conserved aspartate residue (Asp-52) in ArsR, which leads to modification of the ArsR regulatory functions (for review, see Refs.…”