Issue 6, 2017

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

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
17 feb 2017
Accepted
10 apr 2017
First published
19 apr 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 4626-4633

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

Y. Wang, L. Hu, F. Xu, Q. Quan, Y. Lai, W. Xia, Y. Yang, Y. Chang, X. Yang, Z. Chai, J. Wang, I. K. Chu, H. Li and H. Sun, Chem. Sci., 2017, 8, 4626 DOI: 10.1039/C7SC00766C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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