Elucidation of the Metabolic Network of Helicobacter pylori J99 and Malaysian Clinical Strains by Phenotype Microarray

Abstract

Background Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level.Materials and MethodsThe phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes.ResultsWe have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l‐aspartic acid, d‐alanine, and l‐asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium.ConclusionThe phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori.

Gastric metabolomics analysis supportsH. pylori’s catabolism of organic and amino acids in both the corpus and antrum

“…pylori catabolizes a large number of amino acids with the most substantial being alanine, arginine, asparagine, aspartate, glutamate, glutamine, proline, and serine, with studies reporting variation in the use of alanine, glycine, and valine (24,29,33,34). This list is consistent with the amino acids depleted in this work although we did not detect depletion of all of these, and additionally found depletion of tyrosine and the glutamate derivatives N-acetylglutamate and pyroglutamic acid/oxoproline.…”

“…Previous work supports the catabolism of carboxylic acids that we also show are used here. H. pylori can catabolize fumaric acid (30), malic acid (24), and lactic acid (22). Catabolism of carboxylic acids requires first their uptake.…”

“…Only one of these is an essential amino acid-serine, and only for some strains (23). The other amino acids are likely used as H. pylori carbon and nitrogen source, as has been shown for aspartic acid (24). Also used up were several additional carboxylic acids including malic acid, fumaric acid, and citric acid.…”

Helicobacter pylori Biofilm Formation Is Differentially Affected by Common Culture Conditions, and Proteins Play a Central Role in the Biofilm Matrix

“…1B). Additionally, we examined the response to the addition of various H. pylori preferred carbon sources (33) to the media (see Fig. S1 in the supplemental material); again, H. pylori biofilm formation was similar in each supplemented medium.…”

Analysis of change in microRNA expression profiles of lung cancer A549 cells treated with Radix tetrastigma hemsleyani flavonoids

“… 16 , 17 Fructose and mannose metabolisms were also an important cancer-related pathways and were previously found to be upregulated in many cancer cells in several studies, such as breast, lung, and ovarian cancer cells. 18 – 20 Axon guidance pathway genes has been found to have aberrations in pancreatic cancer, neuroblastoma (NB), breast cancer, lung cancer, prostate cancers, melanoma, and leukemia. 21 – 23 Four important enrichment signaling pathways and their DE-miRNA target genes are shown in Figure 7 .…”