Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase
文献类型：期刊论文
| 作者 | Zhang, Jie1; Liu, Hongchuan1; Zhu, Kongkai2; Gong, Shouzhe1; Dramsi, Shaynoor3,4; Wang, Ya-Ting3; Li, Jiafei1; Chen, Feifei1; Zhang, Ruihan2; Zhou, Lu5 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 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. |
| WOS关键词 | GRAM-POSITIVE BACTERIA ; CELL-WALL ; SURFACE-PROTEINS ; ACTIVE-SITE ; ENTEROCOCCUS-FAECALIS ; CLOSTRIDIUM-DIFFICILE ; SUBSTRATE COMPLEX ; UNITED-STATES ; A INHIBITORS ; VIRULENCE |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000341630000065 |
| 出版者 | NATL ACAD SCIENCES |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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