Cell-cycle inhibition by Helicobacter pylori L-asparaginase

Claudia Scotti, Patrizia Sommi, Maria Valentina Pasquetto, Donata Cappelletti, Simona Stivala, Paola Mignosi, Monica Savio, Laurent Roberto Chiarelli, Giovanna Valentini, Victor M. Bolanos-Garcia, Douglas Scott Merrell, Silvia Franchini, Maria Luisa Verona, Cristina Bolis, Enrico Solcia, Rachele Manca, Diego Franciotta, Andrea Casasco, Paola Filipazzi, Elisabetta ZardiniVanio Vannini

Research output: Contribution to journalArticlepeer-review

Abstract

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated 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, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase 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.

Original languageEnglish
Article numbere13892
JournalPLoS One
Volume5
Issue number11
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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