Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Genetic evidence for histidine kinase HP165 being an acid sensor of Helicobacter pylori. 1510 19

The human gastric pathogen Helicobacter pylori is extremely well adapted to the highly acidic conditions encountered in the stomach. The pronounced acid resistance of H. pylori relies mainly on the ammonia-producing enzyme urease; however, urease-independent mechanisms are likely to contribute to acid adaptation. Acid-responsive gene regulation is mediated at least in part by the ArsRS two-component system consisting of the essential OmpR-like response regulator ArsR and the nonessential cognate histidine kinase ArsS, whose autophosphorylation is triggered in response to low pH. In this study, by global transcriptional profiling of an ArsS-deficient H. pylori mutant grown at pH 5.0, we define the ArsR approximately P-dependent regulon consisting of 109 genes, including the urease gene cluster, the genes encoding the aliphatic amidases AmiE and AmiF, and the rocF gene encoding arginase. We show that ArsR approximately P controls the acid-induced transcription of amiE and amiF by binding to extended regions located upstream of the -10 box of the respective promoters. In contrast, transcription of rocF is repressed by ArsR approximately P at neutral, acidic, and mildly alkaline pH via high-affinity binding of the response regulator to a site overlapping the promoter of the rocF gene.
 ...
PMID:Characterization of the ArsRS regulon of Helicobacter pylori, involved in acid adaptation. 1667 98

Urea transporters in bacteria are relatively rare. There are three classes, the ABC transporters such as those expressed by cyanobacteria and Corynebacterium glutamicum, the Yut protein expressed by Yersinia spp and the UreI expressed by gastric Helicobacter spp. This review focuses largely on the UreI proton-gated channel that is part of the acid acclimation mechanism essential for gastric colonization by the latter. UreI is a six-transmembrane polytopic integral membrane protein, N and C termini periplasmic, and is expressed in all gastric Helicobacter spp that have been studied but also in Helicobacter hepaticus and Streptococcus salivarius. The first two are proton-gated, the latter is pH insensitive. Site-directed mutagenesis and chimeric constructs have identified histidines and dicarboxylic amino acids in the second periplasmic loop of H. pylori and the first loop of H. hepaticus UreI and the C terminus of both as involved in a hydrogen-bonding dependence of proton gating, with the membrane domain in these but not in the UreI of S. salivarius responding to the periplasmic conformational changes. UreI and urease are essential for gastric colonization and urease associates with UreI during acid exposure, facilitating activation of the UreA and UreB apoenzyme complex by Ni2+ insertion by the UreF-UreH and UreE-UreG assembly proteins. Transcriptome analysis of acid responses of H. pylori also identified a cytoplasmic and periplasmic carbonic anhydrase as responding specifically to changes in periplasmic pH and these have been shown to be essential also for acid acclimation. The finding also of upregulation of the two-component histidine kinase HP0165 and its response element HP0166, illustrates the complexity of the acid acclimation processes involved in gastric colonization by this pathogen.
 ...
PMID:Urea transport in bacteria: acid acclimation by gastric Helicobacter spp. 1726 89

Helicobacter pylori colonizes the normal human stomach by maintaining both periplasmic and cytoplasmic pH close to neutral in the presence of gastric acidity. Urease activity, urea flux through the pH-gated urea channel, UreI, and periplasmic alpha-carbonic anhydrase are essential for colonization. Exposure to pH 4.5 for up to 180 min activates total bacterial urease threefold. Within 30 min at pH 4.5, the urease structural subunits, UreA and UreB, and the Ni(2+) insertion protein, UreE, are recruited to UreI at the inner membrane. Formation of this complex and urease activation depend on expression of the cytoplasmic sensor histidine kinase, HP0244. Its deletion abolishes urease activation and assembly, impairs cytoplasmic and periplasmic pH homeostasis, and depolarizes the cells, with an approximately 7-log loss of survival at pH 2.5, even in 10 mM urea. Associated with this assembly, UreI is able to transport NH(3), NH(4)(+), and CO(2), as shown by changes in cytoplasmic pH following exposure to NH(4)Cl or CO(2). To be able to colonize cells in the presence of the highly variable pH of the stomach, the organism expresses two pH-sensor histidine kinases, one, HP0165, responding to a moderate fall in periplasmic pH and the other, HP0244, responding to cytoplasmic acidification at a more acidic medium pH. Assembly of a pH-regulatory complex of active urease with UreI provides an advantage for periplasmic buffering.
 ...
PMID:Cytoplasmic histidine kinase (HP0244)-regulated assembly of urease with UreI, a channel for urea and its metabolites, CO2, NH3, and NH4(+), is necessary for acid survival of Helicobacter pylori. 1985 93