Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa
文献类型：期刊论文
| 作者 | Chen, Weizhong2,3; Wang, Dan3; Zhou, Wenquan4; Sang, Hong5; Liu, Xichun3; Ge, Zhiyun3; Zhang, Jin3; Lan, Lefu1 ; Yang, Cai-Guang1; Chen, Hao3,6
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| 刊名 | MOLECULAR MICROBIOLOGY
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| 出版日期 | 2016-06 |
| 卷号 | 100期号:5页码:749-758 |
| ISSN号 | 0950-382X |
| DOI | 10.1111/mmi.13346 |
| 文献子类 | Article |
| 英文摘要 | NalD was reported to be the secondary repressor of the MexAB-OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa. Here, we show that novobiocin binds directly to NalD, which leads NalD to dissociate from the DNA promoter, and thus de-represses the expression of the MexAB-OprM pump. In addition, we have solved the crystal structure of NalD at a resolution of 2.90 angstrom. The structural alignment of NalD to its homologue TtgR reveals that the residues N129 and H167 in NalD are involved in its novobiocin-binding ability. We have confirmed the function of these two amino acids by EMSA and plate assay. The results presented here highlight the importance and diversity of regulatory mechanism in bacterial antibiotic resistance, and provide further insight for novel antimicrobial development. |
| WOS关键词 | MULTIDRUG EFFLUX PUMPS ; MULTIPLE ANTIBIOTIC-RESISTANCE ; OXIDATION-SENSING MECHANISM ; INTRINSIC RESISTANCE ; GENE-EXPRESSION ; REGULATOR MEXR ; REPRESSOR ; OPERON ; TTGR ; IDENTIFICATION |
| 资助项目 | National Nature Science Foundation of China[21071077] ; National Nature Science Foundation of China[91013009] ; National Nature Science Foundation of China[81371782] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507009-01] ; Ministry of Science and Technology of China[2012CB933802] ; Ministry of Science and Technology of China[2015CB856303] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Microbiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000379685800001 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276013]  |
| 专题 | 药理学第三研究室 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 |
| 通讯作者 | Chen, Hao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Sci & Technol China, Dept Chem Phys, Hefei 230026, Peoples R China; 3.Nanjing Univ, State Key Lab Coordinat Chem, Sch Chem & Chem Engn, Collaborat Innovat Ctr Chem Life Sci, Nanjing 210093, Jiangsu, Peoples R China; 4.Nanjing Univ, Sch Med, Jinling Hosp, Dept Urol, Nanjing 210093, Jiangsu, Peoples R China; 5.Nanjing Univ, Sch Med, Jinling Hosp, Dept Dermatol, Nanjing 210093, Jiangsu, Peoples R China; 6.Nanjing Univ, Sch Chem & Chem Engn, Hankou Rd 22, Nanjing 210093, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Weizhong,Wang, Dan,Zhou, Wenquan,et al. Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa[J]. MOLECULAR MICROBIOLOGY,2016,100(5):749-758. |
| APA | Chen, Weizhong.,Wang, Dan.,Zhou, Wenquan.,Sang, Hong.,Liu, Xichun.,...&Chen, Hao.(2016).Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa.MOLECULAR MICROBIOLOGY,100(5),749-758. |
| MLA | Chen, Weizhong,et al."Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa".MOLECULAR MICROBIOLOGY 100.5(2016):749-758. |
入库方式： OAI收割
来源：上海药物研究所
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