A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori
Autor: | Qing Gu, Xuesong Sun, Julian A. Tanner, Rory M. Watt, Hongzhe Sun, Jian-Dong Huang, Harry Huaxiang Xia, Benjamin Chun Yu Wong, Qing-Yu He, Ruiguang Ge |
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Rok vydání: | 2007 |
Předmět: |
Proteomics
inorganic chemicals Proteases medicine.medical_treatment Microbial Sensitivity Tests medicine.disease_cause digestive system Biochemistry Cell Line Inorganic Chemistry chemistry.chemical_compound Bacterial Proteins Nickel Metalloproteins Organometallic Compounds medicine Humans Protease Inhibitors chemistry.chemical_classification Protease Helicobacter pylori biology Chemistry Gene Expression Profiling Gene Expression Regulation Bacterial equipment and supplies bacterial infections and mycoses biology.organism_classification digestive system diseases Enzyme Fumarase Oxidative stress Intracellular Hemin |
Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 12:831-842 |
ISSN: | 1432-1327 0949-8257 |
DOI: | 10.1007/s00775-007-0237-7 |
Popis: | Helicobacter pylori is a major human pathogen that can cause peptic ulcers and chronic gastritis. Bismuth-based triple or quadruple therapies are commonly recommended for the treatment of H. pylori infections. However, the molecular mechanisms underlying treatment with bismuth are currently not fully understood. We have conducted a detailed comparative proteomic analysis of H. pylori cells both before and after treatment with colloidal bismuth subcitrate (CBS). Eight proteins were found to be significantly upregulated or downregulated in the presence of CBS (20 microg mL(-1)). Bismuth-induced oxidative stress was confirmed by detecting higher levels of lipid hydroperoxide (approximately 1.8 times) and hemin (approximately 3.4 times), in whole cell extracts of bismuth-treated H. pylori cells, compared with those from untreated cells. The presence of bismuth also led to an approximately eightfold decrease in cellular protease activities. Using immobilized-bismuth affinity chromatography, we isolated and subsequently identified seven bismuth-binding proteins from H. pylori cell extracts. The intracellular levels of four of these proteins (HspA, HspB, NapA and TsaA) were influenced by the addition of CBS, which strongly suggests that they interact directly with bismuth. The other bismuth-interacting proteins identified were two enzymes (fumarase and the urease subunit UreB), and a translational factor (Ef-Tu). Our data suggest that the inhibition of proteases, modulation of cellular oxidative stress and interference with nickel homeostasis may be key processes underlying the molecular mechanism of bismuth's actions against H. pylori. |
Databáze: | OpenAIRE |
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