World Journal of
Pharmaceutical and Life Sciences

ROLE OF THE GENE HP0102 ENCODING A CONSERVED LPS GLYCOSYLTRANSFERASE IN THE PATHOGENESIS OF HELICOBACTER PYLORI

Suryawanshi Harinath* and Dr. Teelavath Mangilal

ABSTRACT

Helicobacter pylori are a major human pathogen and are associated with chronic gastric inflammation, peptic ulcer disease and gastric cancer. Contact with host cells is recognized as a signal capable of triggering expression of bacterial genes important for host pathogen interaction. Adherence of H. pylori to the gastric epithelial cell lines AGS and MKN45 strongly upregulated expression of a gene HP0102 in the adhered bacteria as determined by qRT-PCR. In silico analysis suggested that HP0102 shows tremendous sequence conservation among different strains of H. pylori including several Indian clinical isolates and was predicted to encode for a glycosyltransferase enzyme. To elucidate the role of HP0102, a HP0102 knockout strain was constructed (?HP0102) and analyzed. The gene was found to be associated with two distinct phenotypes related to pathogenicity. In AGS cell-adhered H. pylori, it has a role in upregulation of cag A, a major virulence factor and consequent induction of the hummingbird phenotype in the infected AGS cells. HP0102 was also found to be involved in the glycosylation of bacterial lipopolysachharides (LPS) by glycostaining analysis. Bacterial LPS is a major virulence factor triggering the expression of cytokines via TLR 2 and TLR4 dependent signaling cascades. Results of a cytokine array using the cell culture supernatants of MKN45 cells (expressing both TLR2 and TLR4) infected with either H. pylori wild type or the ?HP0102 strain suggested that the HP0102 mutant was impaired in inducing the expression of several cytokines including the proinflammatory cytokine IL-8. Further work is under progress to identify more specific functions of HP0102 and also identify other signaling networks that may be affected by LPS and its glycosylation state during the pathogenesis of H. pylori.

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