Distinct transcriptome signatures of Helicobacter suis and Helicobacter heilmannii strains upon adherence to human gastric epithelial cells

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 (p(adj) ≤ 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.