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Bismuth drugs, despite being clinically used for decades, surprisingly remain in use and effective for the treatment of Helicobacter pylori infection, even for resistant strains when co-administrated with antibiotics. However, the molecular mechanisms underlying the clinically sustained susceptibility of H.

Bismuth drugs, despite being clinically used for decades, surprisingly remain in use and effective for the treatment of Helicobacter pylori infection, even for resistant strains when co-administrated with antibiotics. However, the molecular mechanisms underlying the clinically sustained susceptibility of H. pylori to bismuth drugs remain elusive. Herein, we report that integration of in-house metalloproteomics and quantitative proteomics allows comprehensive uncovering of the bismuth-associated proteomes, including 63 bismuth-binding and 119 bismuth-regulated proteins from Helicobacter pylori, with over 60% being annotated with catalytic functions. Through bioinformatics analysis in combination with bioassays, we demonstrated that bismuth drugs disrupted multiple essential pathways in the pathogen, including ROS defence and pH buffering, by binding and functional perturbation of a number of key enzymes. Moreover, we discovered that HpDnaK may serve as a new target of bismuth drugs to inhibit bacterium-host cell adhesion. The integrative approach we report, herein, provides a novel strategy to unveil the molecular mechanisms of antimicrobial metals against pathogens in general. This study sheds light on the design of new types of antimicrobial agents with multiple targets to tackle the current crisis of antimicrobial resistance.

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    Title
    • Integrative Approach for the Analysis of the Proteome-Wide Response to Bismuth Drugs in Helicobacter Pylori
    Contributors
    Date Created
    2017-04-19
    Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.1039/C7SC00766C
    • Identifier Type
      International standard serial number
      Identifier Value
      2041-6520
    • Identifier Type
      International standard serial number
      Identifier Value
      2041-6539
    Note
    • The final version of this article, as published in Chemical Science, can be viewed online at: http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC00766C#!divAbstract

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    This is a suggested citation. Consult the appropriate style guide for specific citation guidelines.

    Wang, Y., Hu, L., Xu, F., Quan, Q., Lai, Y., Xia, W., . . . Sun, H. (2017). Integrative approach for the analysis of the proteome-wide response to bismuth drugs in Helicobacter pylori. Chem. Sci., 8(6), 4626-4633. doi:10.1039/c7sc00766c

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