A Positively Selected -R88H Mutation Enhances Helicobacter pylori Fitness in a High-Salt Environment and Alters Fur-Dependent Regulation of Gene Expression.

Both Helicobacter pylori infection and a high-salt diet are risk factors for gastric cancer. We previously showed that a mutation in (encoding the ferric uptake regulator variant Fur-R88H) was positively selected in H. pylori strains isolated from experimentally infected Mongolian gerbils receiving a high-salt diet.

Positive Selection of Mutations in the Helicobacter pylori 5' Untranslated Region in a Mongolian Gerbil Model of Gastric Disease.

To evaluate potential effects of gastric inflammation on Helicobacter pylori diversification and evolution within the stomach, we experimentally infected Mongolian gerbils with an H. pylori strain in which Cag type IV secretion system (T4SS) activity is controlled by a TetR/ system. Gerbils infected with H.

Enhanced Fitness of a Helicobacter pylori Mutant in a Murine Model.

Helicobacter pylori genomes encode over 60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify mutant strains exhibiting differential fitness compared to , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H.

Delineation of the pH-Responsive Regulon Controlled by the Helicobacter pylori ArsRS Two-Component System.

encounters a wide range of pH within the human stomach. In a comparison of cultured under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in gene expression.

Helicobacter pylori-Induced TLR9 Activation and Injury Are Associated With the Virulence-Associated Adhesin HopQ.

Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma. The H. pylori cancer-associated cag pathogenicity island (cag-PAI) encodes a type IV secretion system (T4SS), which translocates microbial DNA and activates TLR9; however, most cag-PAI+-infected persons do not develop cancer and cag-PAI-independent regulators of pathogenesis, including strain-specific adhesins, remain understudied.

Temporal Control of the Helicobacter pylori Cag Type IV Secretion System in a Mongolian Gerbil Model of Gastric Carcinogenesis.

The Cag type IV secretion system (T4SS) translocates the effector protein CagA and nonprotein bacterial constituents into host cells. In this study, we infected Mongolian gerbils with an strain in which expression of the operon (required for Cag T4SS activity) is controlled by a TetR/ system. Transcript levels of were significantly higher in gastric tissue from -infected animals receiving doxycycline-containing chow (to derepress Cag T4SS activity) than in tissue from infected control animals receiving drug-free chow.

Bacterial Energetic Requirements for Helicobacter pylori Cag Type IV Secretion System-Dependent Alterations in Gastric Epithelial Cells.

colonizes the stomach in about half of the world's population. strains containing the pathogenicity island ( PAI) are associated with a higher risk of gastric adenocarcinoma or peptic ulcer disease than PAI-negative strains. The PAI encodes a type IV secretion system (T4SS) that mediates delivery of the CagA effector protein as well as nonprotein bacterial constituents into gastric epithelial cells.

Effect of environmental salt concentration on the Helicobacter pylori exoproteome.

Helicobacter pylori infection and a high salt diet are each risk factors for gastric cancer. In this study, we tested the hypothesis that environmental salt concentration influences the composition of the H. pylori exoproteome.

Role of a Stem-Loop Structure in Transcript Stability.

CagA is a secreted effector protein that contributes to gastric carcinogenesis. Previous studies showed that there is variation among strains in the steady-state levels of CagA and that a strain-specific motif downstream of the transcriptional start site (the +59 motif) is associated with both high levels of CagA and premalignant gastric histology. The 5' untranslated region contains a predicted stem-loop-forming structure adjacent to the +59 motif.

genetic diversification in the Mongolian gerbil model.

requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed genetic adaptation in the Mongolian gerbil model. This model is of particular interest because -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration.

High-Salt Conditions Alter Transcription of Helicobacter pylori Genes Encoding Outer Membrane Proteins.

infection and high dietary salt intake are risk factors for the development of gastric adenocarcinoma. One possible mechanism by which a high-salt diet could influence gastric cancer risk is by modulating gene expression. In this study, we utilized transcriptome sequencing (RNA-seq) methodology to compare the transcriptional profiles of grown in media containing different concentrations of sodium chloride.

Pan-genomic analyses identify key pathogenic loci modified by carcinogenic host microenvironments.

Objective: is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of to in vivo carcinogenic microenvironments results in genetic modification important for disease.

Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens.

Unlabelled: Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens.

Helicobacter pylori adaptation in vivo in response to a high-salt diet.

Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification of H. pylori is influenced by the composition of the diet.

Alteration of the Helicobacter pylori membrane proteome in response to changes in environmental salt concentration.

Purpose: Helicobacter pylori infection and a high dietary salt intake are each risk factors for the development of gastric cancer. We hypothesize that changes in environmental salt concentrations lead to alterations in the H. pylori membrane proteome.

The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration.

Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters essential nutrient metals away from invading pathogenic bacteria. Neutrophils participate in this process by producing several metal chelating proteins, including lactoferrin and calprotectin (CP).

Flagellar localization of a Helicobacter pylori autotransporter protein.

Unlabelled: Helicobacter pylori contains four genes that are predicted to encode proteins secreted by the autotransporter (type V) pathway. One of these, the pore-forming toxin VacA, has been studied in great detail, but thus far there has been very little investigation of three VacA-like proteins. We show here that all three VacA-like proteins are >250 kDa in mass and localized on the surface of H.

High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis.

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.

Analysis of Helicobacter pylori cagA promoter elements required for salt-induced upregulation of CagA expression.

Helicobacter pylori infection and consumption of a high-salt diet are each associated with an increased risk for the development of gastric cancer. To investigate potential synergism between these factors, we used a global proteomic approach to analyze H. pylori strains cultured in media containing varying salt concentrations.

Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from asymptomatic children.

Background: Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer.

Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface.

Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI) encodes components of a type IV secretion system (T4SS) that translocates the bacterial oncoprotein CagA into gastric epithelial cells, and CagL is a specialized component of the cag T4SS that binds the host receptor α5β1 integrin.

Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.

Background: Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis.

Methods: We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression.

In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription.

Background: LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB), synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H.

Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system.

Previous studies have shown that the Helicobacter pylori ArsRS two-component signal transduction system contributes to acid-responsive gene expression. To identify additional members of the ArsRS regulon and further investigate the regulatory role of the ArsRS system, we analyzed protein expression in wild-type and arsS null mutant strains. Numerous proteins were differentially expressed in an arsS mutant strain compared to a wild-type strain when the bacteria were cultured at pH 5.

Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells.

Helicobacter pylori genomes contain about 30 hop genes that encode outer membrane proteins. Helicobacter pylori hopQ alleles exhibit a high level of genetic diversity, and two families of hopQ alleles have been described. Type I hopQ alleles are found more commonly in cag-positive H.