Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 5 of 5

Publication Record

Connections

Genetic Evolution of a Helicobacter pylori Acid-Sensing Histidine Kinase and Gastric Disease.
Krishna U, Romero-Gallo J, Suarez G, Azah A, Krezel AM, Varga MG, Forsyth MH, Peek RM
(2016) J Infect Dis 214: 644-8
MeSH Terms: Achlorhydria, Acids, Animals, Bacterial Proteins, Evolution, Molecular, Gastritis, Gerbillinae, Helicobacter Infections, Helicobacter pylori, Histidine Kinase, Humans, Male, Mice, Inbred C57BL, Microbial Viability, Mutation, Missense
Show Abstract · Added April 6, 2017
Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, which develops within a hypochlorhydric environment. We sequentially isolated H. pylori (strain J99) from a patient who developed corpus-predominant gastritis and hypochlorhydia over a 6-year interval. Archival J99 survived significantly better under acidic conditions than recent J99 strains. H. pylori arsRS encodes a 2-component system critical for stress responses; recent J99 isolates harbored 2 nonsynonymous arsS mutations, and arsS inactivation abolished acid survival. In vivo, acid-resistant archival, but not recent J99, successfully colonized high-acid-secreting rodents. Thus, genetic evolution of arsS may influence progression to hypochlorhydia and gastric cancer.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion.
Hammond CE, Beeson C, Suarez G, Peek RM, Backert S, Smolka AJ
(2015) Am J Physiol Gastrointest Liver Physiol 309: G193-201
MeSH Terms: Achlorhydria, Antigens, Bacterial, Bacterial Proteins, Cells, Cultured, Epithelial Cells, Gastric Acid, Gastric Mucosa, Helicobacter Infections, Helicobacter pylori, Humans, Interleukin-8, NF-kappa B, Promoter Regions, Genetic, Proton Pumps, Signal Transduction, Sodium-Potassium-Exchanging ATPase, Virulence Factors
Show Abstract · Added February 5, 2016
Acute Helicobacter pylori infection of gastric epithelial cells and human gastric biopsies represses H,K-ATPase α subunit (HKα) gene expression and inhibits acid secretion, causing transient hypochlorhydria and supporting gastric H. pylori colonization. Infection by H. pylori strains deficient in the cag pathogenicity island (cag PAI) genes cagL, cagE, or cagM, which do not transfer CagA into host cells or induce interleukin-8 secretion, does not inhibit HKα expression, nor does a cagA-deficient strain that induces IL-8. To test the hypothesis that virulence factors other than those mediating CagA translocation or IL-8 induction participate in HKα repression by activating NF-κB, AGS cells transfected with HKα promoter-Luc reporter constructs containing an intact or mutated NF-κB binding site were infected with wild-type H. pylori strain 7.13, isogenic mutants lacking cag PAI genes responsible for CagA translocation and/or IL-8 induction (cagA, cagζ, cagε, cagZ, and cagβ), or deficient in genes encoding two peptidoglycan hydrolases (slt and cagγ). H. pylori-induced AGS cell HKα promoter activities, translocated CagA, and IL-8 secretion were measured by luminometry, immunoblotting, and ELISA, respectively. Human gastric biopsy acid secretion was measured by microphysiometry. Taken together, the data showed that HKα repression is independent of IL-8 expression, and that CagA translocation together with H. pylori transglycosylases encoded by slt and cagγ participate in NF-κB-dependent HKα repression and acid inhibition. The findings are significant because H. pylori factors other than CagA and IL-8 secretion are now implicated in transient hypochlorhydria which facilitates gastric colonization and potential triggering of epithelial progression to neoplasia.
Copyright © 2015 the American Physiological Society.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Helicobacter pylori-induced posttranscriptional regulation of H-K-ATPase α-subunit gene expression by miRNA.
Zhang YM, Noto JM, Hammond CE, Barth JL, Argraves WS, Backert S, Peek RM, Smolka AJ
(2014) Am J Physiol Gastrointest Liver Physiol 306: G606-13
MeSH Terms: 3' Untranslated Regions, Achlorhydria, Antigens, Bacterial, Bacterial Proteins, Binding Sites, Cell Line, Gastric Mucosa, Gene Expression Regulation, Enzymologic, Genes, Reporter, H(+)-K(+)-Exchanging ATPase, Helicobacter Infections, Helicobacter pylori, Host-Pathogen Interactions, Humans, MicroRNAs, NF-kappa B p50 Subunit, Parietal Cells, Gastric, Peptidoglycan, RNA Interference, RNA Processing, Post-Transcriptional, RNA, Messenger, Time Factors, Transfection, Virulence
Show Abstract · Added March 10, 2014
Acute Helicobacter pylori infection of gastric epithelial cells induces CagA oncoprotein- and peptidoglycan (SLT)-dependent mobilization of NF-κB p50 homodimers that bind to H-K-ATPase α-subunit (HKα) promoter and repress HKα gene transcription. This process may facilitate gastric H. pylori colonization by induction of transient hypochlorhydria. We hypothesized that H. pylori also regulates HKα expression posttranscriptionally by miRNA interaction with HKα mRNA. In silico analysis of the HKα 3' untranslated region (UTR) identified miR-1289 as a highly conserved putative HKα-regulatory miRNA. H. pylori infection of AGS cells transfected with HKα 3' UTR-Luc reporter construct repressed luciferase activity by 70%, whereas ΔcagA or Δslt H. pylori infections partially abrogated repression. Transfection of AGS cells expressing HKα 3' UTR-Luc construct with an oligoribonucleotide mimetic of miR-1289 induced maximal repression (54%) of UTR activity within 30 min; UTR activity was unchanged by nontargeting siRNA transfection. Gastric biopsies from patients infected with cagA(+) H. pylori showed a significant increase in miR-1289 expression compared with uninfected patients or those infected with cagA(-) H. pylori. Finally, miR-1289 expression was necessary and sufficient to attenuate biopsy HKα protein expression in the absence of infection. Taken together, these data indicate that miR-1289 is upregulated by H. pylori in a CagA- and SLT-dependent manner and targets HKα 3' UTR, affecting HKα mRNA translation. The sensitivity of HKα mRNA 3' UTR to binding of miR-1289 identifies a novel regulatory mechanism of gastric acid secretion and offers new insights into mechanisms underlying transient H. pylori-induced hypochlorhydria.
0 Communities
2 Members
0 Resources
24 MeSH Terms
High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis.
Gaddy JA, Radin JN, Loh JT, Zhang F, Washington MK, Peek RM, Algood HM, Cover TL
(2013) Infect Immun 81: 2258-67
MeSH Terms: Achlorhydria, Adenocarcinoma, Animals, Antigens, Bacterial, Bacterial Proteins, Gastric Mucosa, Gene Expression Regulation, Gerbillinae, H(+)-K(+)-Exchanging ATPase, Helicobacter Infections, Helicobacter pylori, Humans, Hydrogen-Ion Concentration, Inflammation, Interleukin-1beta, Male, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sodium Chloride, Dietary, Stomach, Stomach Neoplasms
Show Abstract · Added January 13, 2014
Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA(+) H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA(+) H. pylori strains.
1 Communities
6 Members
0 Resources
21 MeSH Terms
Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells.
Wang F, Xia P, Wu F, Wang D, Wang W, Ward T, Liu Y, Aikhionbare F, Guo Z, Powell M, Liu B, Bi F, Shaw A, Zhu Z, Elmoselhi A, Fan D, Cover TL, Ding X, Yao X
(2008) J Biol Chem 283: 26714-25
MeSH Terms: Achlorhydria, Actin Cytoskeleton, Animals, Bacterial Proteins, Calcium, Calpain, Cell Membrane, Cell Membrane Permeability, Cells, Cultured, Cytoskeletal Proteins, Gastritis, Atrophic, Helicobacter Infections, Helicobacter pylori, Humans, Parietal Cells, Gastric, Rabbits, Stomach Neoplasms
Show Abstract · Added March 5, 2014
Helicobacter pylori persistently colonize the human stomach and have been linked to atrophic gastritis and gastric carcinoma. Although it is well known that H. pylori infection can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood. Here we show that VacA permeabilizes the apical membrane of gastric parietal cells and induces hypochlorhydria. The functional consequences of VacA infection on parietal cell physiology were studied using freshly isolated rabbit gastric glands and cultured parietal cells. Secretory activity of parietal cells was judged by an aminopyrine uptake assay and confocal microscopic examination. VacA permeabilization induces an influx of extracellular calcium, followed by activation of calpain and subsequent proteolysis of ezrin at Met(469)-Thr(470), which results in the liberation of ezrin from the apical membrane of the parietal cells. VacA treatment inhibits acid secretion by preventing the recruitment of H,K-ATPase-containing tubulovesicles to the apical membrane of gastric parietal cells. Electron microscopic examination revealed that VacA treatment disrupts the radial arrangement of actin filaments in apical microvilli due to the loss of ezrin integrity in parietal cells. Significantly, expression of calpain-resistant ezrin restored the functional activity of parietal cells in the presence of VacA. Proteolysis of ezrin in VacA-infected parietal cells is a novel mechanism underlying H. pylori-induced inhibition of acid secretion. Our results indicate that VacA disrupts the apical membrane-cytoskeletal interactions in gastric parietal cells and thereby causes hypochlorhydria.
0 Communities
1 Members
0 Resources
17 MeSH Terms