Interspecies effectors of a transgenerational memory of bacterial infection in Caenorhabditis elegans

The inheritance of memory is an adaptive trait. Microbes challenge the immunity of organisms and trigger behavioral adaptations that can be inherited, but how bacteria produce inheritance of a trait is unknown. We use Caenorhabditis elegans and its bacteria to study the transgenerational RNA dynamics of interspecies crosstalk leading to a heritable behavior. A heritable response of C. elegans to microbes is the pathogen-induced diapause (PIDF), a state of suspended animation to evade infection. We identify RsmY, a small RNA involved in quorum sensing in Pseudomonas aeruginosa as a trigger of PIDF. The histone methyltransferase (HMT) SET-18/SMYD3 and the argonaute HRDE-1, which promotes multi-generational silencing in the germline, are also needed for PIDF initiation. The HMT SET-25/EHMT2 is necessary for memory maintenance in the transgenerational lineage. Our work is a starting point to understanding microbiome-induced inheritance of acquired traits, and the transgenerational influence of microbes in health and disease.