Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential
Abstract 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 pres...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-12-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114499 |
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| author | Shunyi Zhu Bin Gao Yoshitaka Umetsu Steve Peigneur Ping Li Shinya Ohki Jan Tytgat |
| author_facet | Shunyi Zhu Bin Gao Yoshitaka Umetsu Steve Peigneur Ping Li Shinya Ohki Jan Tytgat |
| author_sort | Shunyi Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a49a93f8b62d4e539800430463584f0a |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Springer Nature |
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| series | EMBO Molecular Medicine |
| spelling | doaj-art-a49a93f8b62d4e539800430463584f0a2025-08-20T03:05:54ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-12-0114212110.15252/emmm.202114499Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potentialShunyi Zhu0Bin Gao1Yoshitaka Umetsu2Steve Peigneur3Ping Li4Shinya Ohki5Jan Tytgat6Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesGroup of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of SciencesCenter for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST)Toxicology and Pharmacology, University of LeuvenKey Laboratory for Biomedical Effects of Nanomaterials and Nanosafety (Chinese Academy of Sciences), National Center for Nanoscience and TechnologyCenter for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST)Toxicology and Pharmacology, University of LeuvenAbstract 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.https://doi.org/10.15252/emmm.202114499actinomycesinadaptive evolutionantimicrobial peptidecell‐wall synthesis inhibitorsystemic therapy |
| spellingShingle | Shunyi Zhu Bin Gao Yoshitaka Umetsu Steve Peigneur Ping Li Shinya Ohki Jan Tytgat Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential EMBO Molecular Medicine actinomycesin adaptive evolution antimicrobial peptide cell‐wall synthesis inhibitor systemic therapy |
| title | Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential |
| title_full | Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential |
| title_fullStr | Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential |
| title_full_unstemmed | Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential |
| title_short | Adaptively evolved human oral actinomyces‐sourced defensins show therapeutic potential |
| title_sort | adaptively evolved human oral actinomyces sourced defensins show therapeutic potential |
| topic | actinomycesin adaptive evolution antimicrobial peptide cell‐wall synthesis inhibitor systemic therapy |
| url | https://doi.org/10.15252/emmm.202114499 |
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