Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase

doi:10.1073/pnas.1408601111

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	Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase
	Zhang, Jie 1; Liu, Hongchuan 1; Zhu, Kongkai 2; Gong, Shouzhe 1; Dramsi, Shaynoor 3,4; Wang, Ya-Ting 3; Li, Jiafei 1; Chen, Feifei 1; Zhang, Ruihan 2; Zhou, Lu 5
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2014-09-16
卷号	111 期号:37 页码:13517-13522
关键词	nosocomial infection LPXTG motif antivirulence computational screening
ISSN号	0027-8424
DOI	10.1073/pnas.1408601111
文献子类	Article
英文摘要	Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequent cause of hospital-acquired infection, which manifests as surgical site infections, bacteremia, and sepsis. Due to drug-resistance, prophylaxis of MRSA infection with antibiotics frequently fails or incites nosocomial diseases such as Clostridium difficile infection. Sortase A is a transpeptidase that anchors surface proteins in the envelope of S. aureus, and sortase mutants are unable to cause bacteremia or sepsis in mice. Here we used virtual screening and optimization of inhibitor structure to identify 3-(4-pyridinyl)-6-(2-sodiumsulfonatephenyl)[1,2,4] triazolo[3,4-b][1,3,4] thiadiazole and related compounds, which block sortase activity in vitro and in vivo. Sortase inhibitors do not affect in vitro staphylococcal growth yet protect mice against lethal S. aureus bacteremia. Thus, sortase inhibitors may be useful as antiinfective therapy to prevent hospital-acquired S. aureus infection in high-risk patients without the side effects of antibiotics.
资助项目	National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" Grant[2013ZX09507-004] ; National Natural Science Foundation of China[91313303] ; National Natural Science Foundation of China[20972173] ; National Natural Science Foundation of China[81230076] ; Hi-Tech Research and Development Program of China[2012AA020302] ; Hi-Tech Research and Development Program of China[2012AA020301] ; National Institute of Allergy and Infectious Diseases[AI038897] ; Computer Network Information Center[00000000] ; Chinese Academy of Sciences[00000000] ; Shanghai Supercomputing Center[00000000]
WOS关键词	GRAM-POSITIVE BACTERIA ; CELL-WALL ; SURFACE-PROTEINS ; ACTIVE-SITE ; ENTEROCOCCUS-FAECALIS ; CLOSTRIDIUM-DIFFICILE ; SUBSTRATE COMPLEX ; UNITED-STATES ; A INHIBITORS ; VIRULENCE
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATL ACAD SCIENCES
WOS记录号	WOS:000341630000065
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276899]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室药理学第三研究室药理学第一研究室
通讯作者	Schneewind, Olaf
作者单位	1.Chinese Acad Sci, Dept Mol Pharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA; 4.Inst Pasteur, Unite Biol Bacteries Pathogenes Gram Positif, CNRS, Equipe Rech Labellisee 3526, F-75724 Paris, France; 5.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jie,Liu, Hongchuan,Zhu, Kongkai,et al. Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(37):13517-13522.
APA	Zhang, Jie.,Liu, Hongchuan.,Zhu, Kongkai.,Gong, Shouzhe.,Dramsi, Shaynoor.,...&Yang, Cai-Guang.(2014).Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111(37),13517-13522.
MLA	Zhang, Jie,et al."Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.37(2014):13517-13522.