ArticleEMBO molecular medicine2022
Adaptively evolved human oral actinomyces-sourced defensins show therapeutic potential.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Actifensin Evolution in the Human Oral Cavity over the Past 100,000 Years.Journal of the American Chemical Society · 2025Article
- From Gut to Heart: Mendelian Randomization Study Reveals the Causal Relationship Between Gut Microbiota and N-Terminal Pro-B-Type Natriuretic Peptide.Anatolian journal of cardiology · 2025Article
- Trans-kingdom conservation of mechanism between bacterial actifensin and eukaryotic defensins.npj antimicrobials and resistance · 2025Article
- The evolutionary novelty of insect defensins: from bacterial killing to toxin neutralization.Cellular and molecular life sciences : CMLS · 2024Article
- Enhancement of SARS-CoV-2 receptor-binding domain activity by two microbial defensins.Frontiers in microbiology · 2023Article
- Mutation-driven parallel evolution in emergence of ACE2-utilizing sarbecoviruses.Frontiers in microbiology · 2023Article
- A Fungal Defensin Inhibiting Bacterial Cell-Wall Biosynthesis with Non-Hemolysis and Serum Stability.Journal of fungi (Basel, Switzerland) · 2022Article
- Mining the bacterial genome to discover new antimicrobial molecules.EMBO molecular medicine · 2022Article
- Adaptively evolved human oral actinomyces-sourced defensins show therapeutic potential.EMBO molecular medicine · 2022Article
- Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering.Frontiers in microbiology · 2022Article
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7 authors at 3 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
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.
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