Abstract

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 ele-gans and its bacteria to study the transgenerational RNA dynamics of interspe-cies crosstalk leading to a heritable behavior. A heritable response of C. elegans to microbes is the pathogen-induced diapause (PIDF), a state of sus-pended 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 pro-motes multi-generational silencing in the germline, are also needed for PIDF initi-ation. The HMT SET-25/EHMT2 is necessary for memory maintenance in the transgenerational lineage. Our work is a starting point to understanding micro-biome-induced inheritance of acquired traits, and the transgenerational influence of microbes in health and disease.