Correction: Cell-Cycle Inhibition by Helicobacter pylori L-Asparaginase

Abstract

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosaassociated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, nonreducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. Lasparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

Alterations in metabolic pathways in gastric epithelial cells infected with Helicobacter pylori

“…Asparaginase also changes asparagine into aspartic acid, so the lower level of asparagine might be also explained by the upregulation of asparaginase activity in the H. pylori-infected AGS cells.Asparagine enhances the proliferation of cancer cells[28], and therefore, asparaginase has been used as an anti-cancer drug. In addition, H. pylori also possesses its own asparaginase, and it was suggested that H. pylori asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cells[29]. Therefore, H.pylori asparaginase might have contributed to the reduction in the level of asparagine seen in the H. pylori-infected AGS cells.…”