| A small mycobacteriophage-derived peptide and its improved isomer restrict mycobacterial infection via dual mycobactericidal-immunoregulatory activities |
| Yang, Y; Liu, Z; He, XQ; Yang, JJ; Wu, J; Yang, HL; Li, M; Qian, Q; Lai, R; Xu, W; Wei, L
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| 2019
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| 发表期刊 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| ISSN | 0021-9258
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| 卷号 | 294期号:19页码:7615-7631 |
| 摘要 | Mycobacteriophages express various peptides/proteins to infect Mycobacterium tuberculosis (M. tb). Particular attention has been paid to mycobacteriophage-derived endolysin proteins. We herein characterized a small mycobacteriophage-derived peptide designated AK15 with potent anti-M. tb activity. AK15 adopted cationic amphiphilic -helical structure, and on the basis of this structure, we designed six isomers with increased hydrophobic moment by rearranging amino acid residues of the helix. We found that one of these isomers, AK15-6, exhibits enhanced anti-mycobacterial efficiency. Both AK15 and AK15-6 directly inhibited M. tb by trehalose 6,6-dimycolate (TDM) binding and membrane disruption. They both exhibited bactericidal activity, cell selectivity, and synergistic effects with rifampicin, and neither induced drug resistance to M. tb. They efficiently attenuated mycobacterial load in the lungs of M. tb-infected mice. We observed that lysine, arginine, tryptophan, and an -helix are key structural requirements for their direct anti-mycobacterial action. Of note, they also exhibited immunomodulatory effects, including inhibition of proinflammatory response in TDM-stimulated or M. tb-infected murine bone marrow-derived macrophages (BMDMs) and M.tb-infected mice and induction of only a modest level of cytokine (tumor necrosis factor (TNF-) and interleukin-6 (IL-6)) production in murine BMDMs and a T-cell cytokine (interferin- (IFN-) and TNF-) response in murine lung and spleen. In summary, characterization of a small mycobacteriophage-derived peptide and its improved isomer revealed that both efficiently restrain M. tb infection via dual mycobactericidal-immunoregulatory activities. Our work provides clues for identifying small mycobacteriophage-derived anti-mycobacterial peptides and improving those that have cationic amphiphilic -helices. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13027
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| 专题 | 科研部门_天然药物功能蛋白质学科组（赖仞）
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推荐引用方式
GB/T 7714 |
Yang, Y,Liu, Z,He, XQ,et al. A small mycobacteriophage-derived peptide and its improved isomer restrict mycobacterial infection via dual mycobactericidal-immunoregulatory activities[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(19):7615-7631.
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| APA |
Yang, Y.,Liu, Z.,He, XQ.,Yang, JJ.,Wu, J.,...&Wei, L.(2019).A small mycobacteriophage-derived peptide and its improved isomer restrict mycobacterial infection via dual mycobactericidal-immunoregulatory activities.JOURNAL OF BIOLOGICAL CHEMISTRY,294(19),7615-7631.
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| MLA |
Yang, Y,et al."A small mycobacteriophage-derived peptide and its improved isomer restrict mycobacterial infection via dual mycobactericidal-immunoregulatory activities".JOURNAL OF BIOLOGICAL CHEMISTRY 294.19(2019):7615-7631.
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