, Volume 25, Issue 1, pp 95–102 | Cite as

Inhibition of fumarase by bismuth(III): implications for the tricarboxylic acid cycle as a potential target of bismuth drugs in Helicobacter pylori

  • Zhuo Chen
  • Qinglu Zhou
  • Ruiguang Ge


Helicobacter pylori causes various gastric diseases, such as gastritis, peptic ulcerations and gastric cancer. Triple therapy combining bismuth compounds with two antibiotics is the cornerstone of the treatment of H. pylori infections. Up to now, the molecular mechanisms by which bismuth inhibits the growth of H. pylori are far from clear. In the bacterial tricarboxylic acid (TCA) cycle, fumarase catalyses the reversible hydration of fumarate to malic acid. Our previous proteomic work indicated that fumarase was capable of bismuth-binding. The interactions as well as the inhibitory effects of bismuth to fumarase have been characterized in this study. The titration of bismuth showed that each fumarase monomer binds one mol equiv of Bi3+, with negligible secondary structural change. Bismuth-binding results in a near stoichiometric inactivation of the enzyme, leading to an apparent non-competitive mechanism as reflected by the Lineweaver–Burk plots. Our collective data indicate that the TCA cycle is a potential molecular target of bismuth drugs in H. pylori.


Helicobacter pylori Fumarase Bismuth Tricarboxylic acid cycle 



5,5′-Dithiobis(2-nitrobenzoic acid)


Fumarate reductase

H. pylori

Helicobacter pylori


Fast protein liquid chromatography


Mass spectrometer


Phosphate-buffered saline


Succinate dehydrogenase


Sodium dodecyl sulfate–polyacrylamide gel electrophoresis


Tricarboxylic acid



The authors thank the anonymous reviewer for insightful comments. This work was supported by National Natural Science Foundation of China (20801061), Guangdong Natural Science Foundation (8451027501001233) and the Fundamental Research Funds for the Central Universities (10lgpy19).


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.The Laboratory of Integrative Biosciences, College of Life SciencesSun Yat-Sen UniversityGuangzhouChina

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