A mycobacteriophage-derived trehalose-6,6 '-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities
文献类型:期刊论文
作者 | Wei L1,2; Wu J1,3; Liu HQ1,3; Yang HL1; Rong MQ1; Li DS1; Zhang PH4; Han JY[*]5; Lai R[*]1,2 |
刊名 | FASEB JOURNAL
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出版日期 | 2013 |
卷号 | 27期号:8页码:3067-3077 |
关键词 | Mycobacterium tuberculosis cord factor immunoregulative effects cytokine mouse model |
通讯作者 | han_junyou@126.com ; rlai@mail.kiz.ac.cn |
英文摘要 | Bacteriophages, the viruses of eubacteria, have developed unique mechanisms to interact with their host bacteria. They have been viewed as potential antibacterial therapeutics. Mycobacteriophage-derived compounds may interact with Mycobacterium tuberculosis (MTB) and/or its components, such as the cord factor, trehalose-6,6'-dimycolate (TDM), which is the most abundant glycolipid produced on the surface of MTB. TDM emulsion injected intravenously into mice induces lung immunopathology that mimics many aspects of MTB infection. Thus, TDM is an important target for anti-MTB agent development. On the basis of genomics information of mycobacteriophages, 200 peptides were synthesized. Their effects on MTB, their interactions with TDM, and anti-inflammatory activities were tested. One of them (PK34) showed MTB-killing activity with a minimal inhibitory concentration of 50 g/ml and TDM-binding ability. In a mouse model, PK34 showed comparable ability to clear MTB as rifampin did in vivo. It also exerted strong activity to inhibit MTB or TDM-induced inflammation in vivo. PK34 significantly inhibited inflammatory cytokines secretions by inactivating MAPK and PKB signals while it maintained certain proinflammatory cytokine production. It is possible to prospect for TDM-binding and/or anti-MTB peptides by mining the mycobacteriophages genome. In addition to its direct MTB-killing ability, PK34 might be a useful adjunct in the treatment of granulomatous inflammation occurring during mycobacterial infection or a template for developing antituberculosis (TB) agents because of its immunoregulative effects. As a TDM-binding peptide, PK34 may be a promising tool to study TDM's interactions with corresponding receptors and signal pathways. |
收录类别 | SCI |
资助信息 | This work was supported by the Chinese National Natu- ral Science Foundation (30830021, 31025025, 31070701, 31000960, 31025025, U1132601), the Ministry of Science and Technology (2010CB529800, 2009ZX09103-1/091, 2011ZX09102- 002-10), the Ministry of Agriculture (2009ZX08009-159B), and Yunnan Province (Y103951111). |
语种 | 英语 |
WOS记录号 | WOS:000329877600014 |
公开日期 | 2014-06-18 |
源URL | [http://159.226.149.42:8088/handle/152453/7909] ![]() |
专题 | 昆明动物研究所_动物毒素室 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences and Yunan Province, Kunming Institute of Zoology, Kunming, China 2.Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Life Sciences College, Nanjing Agricultural University, Nanjing, China 3.Graduate School of the Chinese Academy of Sciences, Beijing, China 4.Jiangsu Center for New Drug Screening and National Drug Screening Laboratory, China Pharmaceutical University, Nanjing, China 5.Jilin University, Changchun, China |
推荐引用方式 GB/T 7714 | Wei L,Wu J,Liu HQ,et al. A mycobacteriophage-derived trehalose-6,6 '-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities[J]. FASEB JOURNAL,2013,27(8):3067-3077. |
APA | Wei L.,Wu J.,Liu HQ.,Yang HL.,Rong MQ.,...&Lai R[*].(2013).A mycobacteriophage-derived trehalose-6,6 '-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities.FASEB JOURNAL,27(8),3067-3077. |
MLA | Wei L,et al."A mycobacteriophage-derived trehalose-6,6 '-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities".FASEB JOURNAL 27.8(2013):3067-3077. |
入库方式: OAI收割
来源:昆明动物研究所
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