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

doi:10.1039/c7sc00766c

	Integrative approach for the analysis of the proteome-wide response to bismuth drugs in Helicobacter pylori
	Wang, YC; Hu, LG; Xu, F; Quan, Q; Lai, YT; Xia, W; Yang, Y; Chang, YY; Yang, XM; Chai, ZF
刊名	CHEMICAL SCIENCE
	2017
卷号	8 期号:6 页码:4626-4633
ISSN号	2041-6520
DOI	10.1039/c7sc00766c
文献子类	Article
英文摘要	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.
电子版国际标准刊号	2041-6539
WOS关键词	METAL AFFINITY-CHROMATOGRAPHY ; BINDING PROTEINS ; MASS-SPECTROMETRY ; CELLS ; IDENTIFICATION ; RESISTANCE ; NETWORKS ; METALLOPROTEOMICS ; SUSCEPTIBILITY ; ERADICATION
WOS研究方向	Chemistry
语种	英语
WOS记录号	WOS:000402384900056
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/285210]
专题	高能物理研究所_多学科研究中心高能物理研究所_加速器中心
作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Wang, YC,Hu, LG,Xu, F,et al. Integrative approach for the analysis of the proteome-wide response to bismuth drugs in Helicobacter pylori[J]. CHEMICAL SCIENCE,2017,8(6):4626-4633.
APA	Wang, YC.,Hu, LG.,Xu, F.,Quan, Q.,Lai, YT.,...&柴之芳.(2017).Integrative approach for the analysis of the proteome-wide response to bismuth drugs in Helicobacter pylori.CHEMICAL SCIENCE,8(6),4626-4633.
MLA	Wang, YC,et al."Integrative approach for the analysis of the proteome-wide response to bismuth drugs in Helicobacter pylori".CHEMICAL SCIENCE 8.6(2017):4626-4633.