Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle of Pseudomonas aeruginosa for Antibiotic Therapy
文献类型：期刊论文
| 作者 | Feng, Chao5; Huang, Yinong6; He, Wangxiao7; Cheng, Xiyao8; Liu, Huili2; Huang, Yongqi8; Ma, Bohan5; Zhang, Wei7; Liao, Chongbing; Wu, Weihui3 |
| 刊名 | ACS CENTRAL SCIENCE
 |
| 出版日期 | 2019-07-24 |
| 卷号 | 5期号:7页码:1278-1288 |
| ISSN号 | 2374-7943 |
| DOI | 10.1021/acscentsci.9b00452 |
| 英文摘要 | The type 3 secretion system (T3SS) found as cellsurface appendages of many pathogenic Gram-negative bacteria, although nonessential for bacterial survival, is an important therapeutic target for drug discovery and development aimed at inhibiting bacterial virulence without inducing antibiotic resistance. We designed a fluorescence-polarization-based assay for high-throughput screening as a mechanistically well-defined general strategy for antibiotic discovery targeting the T3SS and made a serendipitous discovery of a subset of tanshinones-natural herbal compounds in traditional Chinese medicine widely used for the treatment of cardiovascular and cerebrovascular diseases-as effective inhibitors of the biogenesis of the T3SS needle of multidrug- resistant Pseudomonas aeruginosa. By inhibiting the T3SS needle assembly and, thus, cytotoxicity and pathogenicity, selected tanshinones reduced the secretion of bacterial virulence factors toxic to macrophages in vitro, and rescued experimental animals challenged with lethal doses of Pseudomonas aeruginosa in a murine model of acute pneumonia. As first-in-class inhibitors with a demonstrable safety profile in humans, tanshinones may be used directly to alleviate Pseudomonas-aeruginosaassociated pulmonary infections without inducing antibiotic resistance. Since the T3SS is highly conserved among Gramnegative bacteria, this antivirulence strategy may be applicable to the discovery and development of novel classes of antibiotics refractory to existing resistance mechanisms for the treatment of many bacterial infections. |
| WOS关键词 | III PROTEIN SECRETION ; CORNEAL EPITHELIAL-CELLS ; FLUORESCENCE POLARIZATION ; VIRULENCE ; EXOS ; CHEMISTRY ; COMPLEX ; NICHE ; MODEL |
| 资助项目 | National Institutes of Health of USA[R01GM106710] ; National Institutes of Health of USA[R01CA219150] ; National Natural Science Foundation of China[31770146] ; Natural Science Foundation of Shaanxi Province of China[2017ZDJC-02] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000476928300021 |
| 出版者 | AMER CHEMICAL SOC |
| 资助机构 | National Institutes of Health of USA ; National Institutes of Health of USA ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Shaanxi Province of China ; Natural Science Foundation of Shaanxi Province of China ; National Institutes of Health of USA ; National Institutes of Health of USA ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Shaanxi Province of China ; Natural Science Foundation of Shaanxi Province of China ; National Institutes of Health of USA ; National Institutes of Health of USA ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Shaanxi Province of China ; Natural Science Foundation of Shaanxi Province of China ; National Institutes of Health of USA ; National Institutes of Health of USA ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Shaanxi Province of China ; Natural Science Foundation of Shaanxi Province of China |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/14720]  |
| 专题 | 中国科学院武汉物理与数学研究所 |
| 通讯作者 | Huang, Yinong; Su, Zhengding; Lu, Wuyuan |
| 作者单位 | 1.Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA 2.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 3.Nankai Univ, State Key Lab Med Chem Biol, Key Lab Mol Microbiol & Technol, Minist Educ,Dept Microbiol,Coll Life Sci, Tianjin 300071, Peoples R China 4.Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA 5.Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Ctr Translat Med, Xian 710054, Shaanxi, Peoples R China 6.Xi An Jiao Tong Univ, Affiliated Childrens Hosp, Shaanxi Inst Pediat Dis, Xian 710054, Shaanxi, Peoples R China 7.Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710054, Shaanxi, Peoples R China 8.Hubei Univ Technol, Dept Biol & Food Engn, Wuhan 430068, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Chao,Huang, Yinong,He, Wangxiao,et al. Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle of Pseudomonas aeruginosa for Antibiotic Therapy[J]. ACS CENTRAL SCIENCE,2019,5(7):1278-1288. |
| APA | Feng, Chao.,Huang, Yinong.,He, Wangxiao.,Cheng, Xiyao.,Liu, Huili.,...&Lu, Wuyuan.(2019).Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle of Pseudomonas aeruginosa for Antibiotic Therapy.ACS CENTRAL SCIENCE,5(7),1278-1288. |
| MLA | Feng, Chao,et al."Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle of Pseudomonas aeruginosa for Antibiotic Therapy".ACS CENTRAL SCIENCE 5.7(2019):1278-1288. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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