Abstract
The porcine Helicobacter suis and canine-feline H. heilmannii are gastric Helicobacter species with zoonotic potential. However, little is known about the pathogenesis of human infections with these Helicobacter species. To gain more insight into the interactions of both zoonotic Helicobacter species with human gastric epithelial cells, we investigated bacterial genes that are differentially expressed in a H. suis and H. heilmannii strain after adhesion to the human gastric epithelial cell line MKN7. In vitro Helicobacter-MKN7 binding assays were performed to obtain bacterial RNA for sequencing analysis. H. suis and H. heilmannii bacteria attached to the gastric epithelial cells (i.e. cases) as well as unbound bacteria (i.e. controls) were isolated, after which prokaryotic RNA was purified and sequenced. Differentially expressed genes were identified using the DESeq2 package and SARTools pipeline in R. A list of 134 (83 up-regulated and 51 down-regulated) and 143 (60 up-regulated and 83 down-regulated) differentially expressed genes (padj ≤ 0.01; fold change ≥ 2) were identified for the adherent H. suis and H. heilmannii strains, respectively. According to BLASTp analyses, only 2 genes were commonly up-regulated and 4 genes commonly down-regulated in both pathogens. Differentially expressed genes of the H. suis and H. heilmannii strains belonged to multiple functional classes, indicating that adhesion of both strains to human gastric epithelial cells evokes pleiotropic adaptive responses. Our results suggest that distinct pathways are involved in human gastric colonization of H. suis and H. heilmannii. Further research is needed to elucidate the clinical significance of these findings.
Highlights
Helicobacter (H.) pylori is the best studied gastric Helicobacter species naturally colonizing more than half of the world’s human population
Binding capacity of H. suis and H. heilmannii to MKN7 cells A quantitative fluorescence-based adherence assay was performed to compare binding capacity of H. suis HS1 and H. heilmannii ASB1 to human gastric MKN7 cells. Results to those having a padj ≤ 0.01 and a fold change of at least 2, a list of 134 (Additional files 1, 2) differentially expressed genes between case and control groups was obtained. 83 genes were up-regulated (Additional file 1) and 51 were down-regulated (Additional file 2) upon binding to MKN7 cells compared to unbound bacteria
Comparative analysis between differentially expressed H. suis and H. heilmannii genes according to gene function The differentially expressed genes in H. suis and H. heilmannii upon adherence to MKN7 cells compared to unbound bacteria were classified by function, as shown in Figure 6 and Additional files 11, 12, 13, 14
Summary
Helicobacter (H.) pylori is the best studied gastric Helicobacter species naturally colonizing more than half of the world’s human population. It is responsible for a wide range of gastric pathologies, including cancer [1, 2]. Other spiral-shaped non-H. pylori Helicobacter species (NHPH) have been demonstrated to colonize the human gastric mucosa as well. Their prevalence in humans ranges from 0.1 to 6.2% [3,4,5], with a higher density in Asia compared to Europe [5,6,7]. Transmission from animals to humans may occur through direct or indirect contact with infected animals, and, in case of H. suis, via consumption of raw or undercooked pork [8, 10]
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