38th Annual Meeting of the Society for Invertebrate Pathology

Pore-forming toxins (PFTs) constitute one of the most important single classes of bacterial virulence factors. Bacillus thuringiensis (Bt) crystal (Cry) toxins are PFTs famous for their ability to target insects and nematodes. We are using the interaction of Bt and Bt Cry toxins with the genetically-tractable nematode C. elegans to study how animals respond to and defend against PFTs and pathogenic Bacilli.

Using Affymetrix gene chips, we have shown that the C. elegans transcriptome responds rapidly and robustly to PFT. One of the pathways up-regulated is p38, a pathway important for innate immunity in mammals. Loss of p38 in C. elegans leads to animals that are hypersensitive to attack by Crystal toxin. The p38 pathway is also shown to play an important role in defending mammalian cell systems against PFTs. We identified 3 downstream targets of the p38 pathway, some of which are important for protecting C. elegans against PFTs made by mammalian pathogens. We are exploring whether and how the p38 pathway is activated in response to PFT.

Independently, we are using forward and reverse genetics and are uncovering many new genes and pathways involved in defense against PFTs. Our goal is to understand how animals defend against intoxication by PFTs.