Cell-cycle inhibition by Helicobacter pylori L-asparaginase |
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Authors: | Scotti Claudia Sommi Patrizia Pasquetto Maria Valentina Cappelletti Donata Stivala Simona Mignosi Paola Savio Monica Chiarelli Laurent Roberto Valentini Giovanna Bolanos-Garcia Victor M Merrell Douglas Scott Franchini Silvia Verona Maria Luisa Bolis Cristina Solcia Enrico Manca Rachele Franciotta Diego Casasco Andrea Filipazzi Paola Zardini Elisabetta Vannini Vanio |
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Institution: | Department of Experimental Medicine, Section of General Pathology, University of Pavia, Pavia, Italy. claudia.scotti@unipv.it |
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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. |
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