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

ABSTRACT: Helicobacter pylori 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 H. pylori gene expression. In this study, we utilized transcriptome sequencing (RNA-seq) methodology to compare the transcriptional profiles of H. pylori grown in media containing different concentrations of sodium chloride. We identified 118 differentially expressed genes (65 upregulated and 53 downregulated in response to high-salt conditions), including multiple members of 14 operons. Twenty-nine of the differentially expressed genes encode proteins previously shown to undergo salt-responsive changes in abundance, based on proteomic analyses. Real-time reverse transcription (RT)-PCR analyses validated differential expression of multiple genes encoding outer membrane proteins, including adhesins (SabA and HopQ) and proteins involved in iron acquisition (FecA2 and FecA3). Transcript levels of sabA, hopA, and hopQ are increased under high-salt conditions, whereas transcript levels of fecA2 and fecA3 are decreased under high-salt conditions. Transcription of sabA, hopA, hopQ, and fecA3 is derepressed in an arsS mutant strain, but salt-responsive transcription of these genes is not mediated by the ArsRS two-component system, and the CrdRS and FlgRS two-component systems do not have any detectable effects on transcription of these genes. In summary, these data provide a comprehensive view of H. pylori transcriptional alterations that occur in response to high-salt environmental conditions.

SUBMITTER: Loh JT

PROVIDER: S-EPMC5820969 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Loh John T JT Beckett Amber C AC Scholz Matthew B MB Cover Timothy L TL

Infection and immunity 20180220 3

Helicobacter pylori 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 H. pylori gene expression. In this study, we utilized transcriptome sequencing (RNA-seq) methodology to compare the transcriptional profiles of H. pylori grown in media containing different concentrations of sodium chloride. We identified 118 differentia ...[more]

PMID: 29229727

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Project description:In the past decade, researchers have proposed that the pldA gene for outer membrane phospholipase A (OMPLA) is important for bacterial colonization of the human gastric ventricle. Several conserved Helicobacter pylori genes have distinct genotypes in different parts of the world, biogeographic patterns that can be analyzed through phylogenetic trees. The current study will shed light on the importance of the pldA gene in H. pylori. In silico sequence analysis will be used to investigate whether the bacteria are in the process of preserving, optimizing, or rejecting the pldA gene. The pldA gene will be phylogenetically compared to other housekeeping (HK) genes, and a possible origin via horizontal gene transfer (HGT) will be evaluated through both intra- and inter-species evolutionary analyses.In this study, pldA gene sequences were phylogenetically analyzed and compared with a large reference set of concatenated HK gene sequences. A total of 246 pldA nucleotide sequences were used; 207 were from Norwegian isolates, 20 were from Korean isolates, and 19 were from the NCBI database. Best-fit evolutionary models were determined with MEGA5 ModelTest for the pldA (K80 + I + G) and HK (GTR + I + G) sequences, and maximum likelihood trees were constructed. Both HK and pldA genes showed biogeographic clustering. Horizontal gene transfer was inferred based on significantly different GC contents, the codon adaptation index, and a phylogenetic conflict between a tree of OMPLA protein sequences representing 171 species and a tree of the AtpA HK protein for 169 species. Although a vast majority of the residues in OMPLA were predicted to be under purifying selection, sites undergoing positive selection were also found.Our findings indicate that the pldA gene could have been more recently acquired than seven of the HK genes found in H. pylori. However, the common biogeographic patterns of both the HK and pldA sequences indicated that the transfer occurred long ago. Our results indicate that the bacterium is preserving the function of OMPLA, although some sites are still being evolutionarily optimized.

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

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

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