Integrative approach for the analysis of the proteome-wide response to bismuth drugs in: Helicobacter pylori

Yuchuan Wang, Ligang Hu, Feng Xu, Quan Quan, Yau Tsz Lai, Wei Xia, Ya Yang, Yuen Yan Chang, Xinming Yang, Zhifang Chai, Junwen Wang, Ivan K. Chu, Hongyan Li, Hongzhe Sun

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4626-4633
Number of pages8
JournalChemical Science
Volume8
Issue number6
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Chemistry(all)

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    Wang, Y., Hu, L., Xu, F., Quan, Q., Lai, Y. T., Xia, W., Yang, Y., Chang, Y. Y., Yang, X., Chai, Z., Wang, J., Chu, I. K., Li, H., & Sun, H. (2017). Integrative approach for the analysis of the proteome-wide response to bismuth drugs in: Helicobacter pylori. Chemical Science, 8(6), 4626-4633. https://doi.org/10.1039/c7sc00766c