The binary toxins Photorhabdus insect-related toxins A and B (PirA and PirB) were first reported in the entomopathogenic bacterium Photorhabdus luminescens. Functionally, PirA/PirB has insecticidal activity against caterpillars of the moth Galleria mellonella, as well as larvae of the mosquitoes Aedes aegypti and Aedes albopictus. Additionally, although genetically distant, PirA and PirB homologs were also found in other insect pathogens such as Photorhabdus asymbiotica and Xenorhabdus doucetiae, and a shrimp pathogen Vibrio parahaemolyticus. However, although it has been established that Photorhabdus PirA/PirB is an effective insecticidal binary toxin, the cytotoxic mechanism remains unclear. In a previous study, we indetified the first crystal structures of PirA/PirB toxins: V. parahaemolyticus PirAvp and PirBvp. The structural analysis indicated a relationship between B. thuringiensis Cry (a three-domain, pore-forming toxin) and PirAvp/PirBvp toxins. Based on this structural similarity, we proposed that PirAvp/PirBvp might use Cry-like pathways, including carbohydrate/receptor binding, oligomerization and pore forming, to induce cell death. However, the hypothesis is yet to be verified. In this proposal, we aim to explore the cytotoxic mechanism of another PirA/PirB toxin: P. luminescens PirApl and PirBpl by structural and proteomic approaches. In addition to solving the crystal structures of PirApl, PirBpl and their complex, we also seek to identify the PirApl/PirBpl receptors as well as PirApl-bound target carbohydrates on the insect cell. Finally, cytotoxicity assays will also be carried out to verify the above results. We expect the findings of this work will extend our understanding of the Pir toxin family, and they may blaze a new way for insecticidal applications of these proteins as well.
|Effective start/end date||8/1/18 → 7/31/19|
- Photorhabdus insect-related toxin
- PirA/PirB binary toxin
- Cry toxin
- bacterial insecticidal toxins
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