A small RNA from a natural bacterial pathogen of C. elegans induces transgenerational inheritance of learned avoidance

A small RNA from a clinical isolate of Pseudomonas aeruginosa, PA14, induces learned avoidance and its transgenerational inheritance in C. elegans . However, it is not known if small RNAs from bacteria found in C. elegans’ natural habitat can regulate host behavior and produce heritable behavioral effects. Here we found that GRb0427, a pathogenic Pseudomonas vranovensis strain isolated from the C. elegans microbiota, similarly affects worm behavior: worms learn to avoid this pathogenic bacterium following exposure, and this learned avoidance is inherited for four generations. The learned response is entirely mediated by small RNAs, which induce avoidance and transgenerational inheritance in both the laboratory N2 strain and a natural isolate of C. elegans , JU1580, providing further support that such mechanisms of learning and inheritance exist in the wild. A small RNA, Pv1, matches the sequence of C. elegans maco-1, and is both necessary and sufficient to induce learned avoidance in worms. However, Pv1 also results in avoidance of a beneficial microbiome strain, P. mendocina ; this maladaptive response may favor reversal of the transgenerational memory after a few generations. Our findings suggest that bacterial small RNA-mediated regulation of host behavior and its transgenerational inheritance are functional in C. elegans’ natural environment, and that different bacterial small RNA-mediated regulation systems evolved independently but define shared molecular features of bacterial small RNAs that produce transgenerationally-inherited effects. ### Competing Interest Statement ZG is the founder of ArrePath