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<p><i>Streptomyces</i> and insects engage in complex interactions shaped by millions of years of evolution. While many beneficial relationships are well recognized, it remains unknown whether <i>Streptomyces</i> produce virulence factors targeting insects specifically. Here, through bioinformatic analysis, we identified diphtheria toxin (DT) homologues, which we named <i>Streptomyces</i> antiquus insecticidal proteins (SAIP), within a monophyletic lineage of <i>Streptomyces</i> that emerged more than 100 million years ago. SAIP is cytotoxic to insect cells and lethal to <i>Drosophila melanogaster</i>, suppressing neuronal activity and immune responses in vivo. Structural and functional studies validated that SAIP is homologous to DT and acts by ADP ribosylation of eukaryotic elongation factor 2. CRISPR–Cas9 screening identified the insect protein Flower as the SAIP receptor across a range of insects. Toxigenic <i>Streptomyces</i> can consume dead insects and produce bioactive secondary metabolites while growing on insect carcasses. These findings establish an insecticidal toxin in <i>Streptomyces</i> and demonstrate that <i>Streptomyces</i> have evolved highly specific virulence factors against insects.</p>

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Streptomyces produce a diphtheria toxin-like exotoxin that targets insects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Ying Xu,
  • Reed M. Stubbendieck,
  • Raghuvir Viswanatha,
  • Ajda Krč,
  • Lisa S. Baik,
  • Won Se Suh,
  • Yanhui Hu,
  • Huan Wang,
  • Linxiang Yin,
  • Enzo Mameli,
  • Anne van der Meij,
  • John R. Carlson,
  • Andrew C. Doxey,
  • Pål Stenmark,
  • Norbert Perrimon,
  • Cameron R. Currie,
  • Min Dong

摘要

Streptomyces and insects engage in complex interactions shaped by millions of years of evolution. While many beneficial relationships are well recognized, it remains unknown whether Streptomyces produce virulence factors targeting insects specifically. Here, through bioinformatic analysis, we identified diphtheria toxin (DT) homologues, which we named Streptomyces antiquus insecticidal proteins (SAIP), within a monophyletic lineage of Streptomyces that emerged more than 100 million years ago. SAIP is cytotoxic to insect cells and lethal to Drosophila melanogaster, suppressing neuronal activity and immune responses in vivo. Structural and functional studies validated that SAIP is homologous to DT and acts by ADP ribosylation of eukaryotic elongation factor 2. CRISPR–Cas9 screening identified the insect protein Flower as the SAIP receptor across a range of insects. Toxigenic Streptomyces can consume dead insects and produce bioactive secondary metabolites while growing on insect carcasses. These findings establish an insecticidal toxin in Streptomyces and demonstrate that Streptomyces have evolved highly specific virulence factors against insects.