| 论文题目： | Adaptively Evolved Human Oral Actinomyces-Sourced Defensins Show Therapeutic Potential |
| 论文题目英文： | |
| 作者： | Zhu, Shunyi; Gao, Bin ; Umetsu, Yoshitaka ; Peigneur, Steve ; Li, Ping ; Ohki, Shinya ; Tytgat, Jan |
| 论文出处： | |
| 年： | 2021 |
| 卷： | 14 |
| 期： | 2 |
| 页： | |
| 联系作者： | 朱顺义 |
| 发表期刊： | EMBO Molecular Medicine |
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| 论文连接 | https://www.embopress.org/doi/full/10.15252/emmm.202114499 |
| 影响因子： | 14.26 |
| 摘要: | The development of eukaryote-derived antimicrobial peptides as systemically administered drugs has proven a challenging task. Here, we report the first human oral actinomyces-sourced defensin-actinomycesin-that shows promise for systemic therapy. Actinomycesin and its homologs are only present in actinobacteria and myxobacteria, and share similarity with a group of ancient invertebrate-type defensins reported in fungi and invertebrates. Signatures of natural selection were detected in defensins from the actinomyces colonized in human oral cavity and ruminant rumen and dental plaque, highlighting their role in adaptation to complex multispecies bacterial communities. Consistently, actinomycesin exhibited potent antibacterial activity against oral bacteria and clinical isolates of Staphylococcus and synergized with two classes of human salivary antibacterial factors. Actinomycesin specifically inhibited bacterial peptidoglycan synthesis and displayed weak immunomodulatory activity and low toxicity on human and mammalian cells and ion channels in the heart and central nervous system. Actinomycesin was highly efficient in mice infected with Streptococcus pneumoniae and mice with MRSA-induced experimental peritoneal infection. This work identifies human oral bacteria as a new source of systemic anti-infective drugs. |
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