Identification and characterization of botulinum neurotoxin–like two-component toxins in <i>Paeniclostridium ghonii</i>
Insecticidal bacterial proteins play key roles in insect-bacteria interactions and have been used as biopesticides. Here, we identify two insecticidal proteins in <i>Paeniclostridium ghonii</i>, designated PG-toxin 1 (PG1) and PG-toxin 2 (PG2), which are homologs of botulinum neurotoxins (BoNTs). Unlike BoNTs, PG1 and PG2 contain two separate proteins: One is the protease light chain (LC), and the other is the heavy chain containing the translocation domain and the receptor binding domain. Crystal and cryo-electron microscopy structures show a conserved BoNT-like architecture but without an interchain disulfide bond. Functional characterizations establish that the LCs of PG1 and PG2 cleave insect synaptosomal-associated protein 25 (SNAP25), but not human or rat SNAP25, and microinjection of PG1 and PG2 caused paralysis and death in <i>Drosophila</i> and <i>Aedes</i> mosquitoes. These findings identified unique two-component BoNT-like insecticidal proteins, revealing insights into the evolution of the BoNT family of toxins, and broadening our understanding of bacteria that can be used for biopest controls.
Authors
- Pyung‐Gang Lee (ORCID: https://orcid.org/0000-0001-9895-1098)
- Briallen Lobb (ORCID: https://orcid.org/0000-0001-7921-0972)
- Michael J. Mansfield (ORCID: https://orcid.org/0000-0003-4717-4721)
- Geoffrey Masuyer (ORCID: https://orcid.org/0000-0002-9527-2310)
- Sarjeet S. Gill (ORCID: https://orcid.org/0000-0002-2273-2304)
- Sabine Pellett (ORCID: https://orcid.org/0000-0001-8186-8810)
- Linxiang Yin (ORCID: https://orcid.org/0000-0002-9884-8194)
- Andrew C. Doxey (ORCID: https://orcid.org/0000-0003-2015-099X)
- Pål Stenmark (ORCID: https://orcid.org/0000-0003-4777-3417)
- Xin Wei (ORCID: https://orcid.org/0000-0001-9219-4575)
- Jingyuan Shi (ORCID: https://orcid.org/0000-0002-0396-3238)
- Sara Košenina (ORCID: https://orcid.org/0000-0001-7893-0249)
- Min Dong (ORCID: https://orcid.org/0000-0002-1744-7293)
- Travis G. Wentz (ORCID: https://orcid.org/0000-0002-1426-7406)
- Haonan Zhang (ORCID: https://orcid.org/0000-0003-3045-3601)
- Ying Xu (ORCID: https://orcid.org/0000-0002-8888-786X)
- Pengsheng Chen (ORCID: https://orcid.org/0000-0003-1577-8854)
- Jack N. Liang (ORCID: https://orcid.org/0009-0007-5757-694X)
Institutions
- University of California, Riverside (US)
- Boston Children's Hospital (US)
- University of Wisconsin–Madison (US)
- Harvard University (US)
- University of Waterloo (CA)
- Stockholm University (SE)
Publication Details
- Journal
- Science Advances
- Published
- 2025-11-12
- DOI
- https://doi.org/10.1126/sciadv.adx6145
- Citations
- 3
- Primary Topic
- Botulinum Toxin and Related Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 4.17