A natural bacterial pathogen of C. elegans uses a small RNA to induce transgenerational inheritance of learned avoidance

A small RNA from 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 similarly regulate host behavior and produce heritable effects. Here we found that GRb0427, a pathogenic Pseudomonas vranovensis strain isolated from the C. elegans microbiota, produces similar effects in C. elegans. Worms are naively attracted to P. vranovensis but learn to avoid this pathogenic bacterium following exposure, and this learned avoidance is transgenerationally inherited by four generations of progeny. The learned response is entirely mediated by small RNAs and is associated with neuronal gene expression changes distinct from the metabolite-driven neuronal changes caused by PA14 exposure. GRb0427 small RNAs induce avoidance and its inheritance not only in the laboratory bred N2 worm strain but also in a natural isolate of C. elegans, JU1580, providing further support that such mechanisms of learning and inheritance likely 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. Our study identifies and characterizes an example of bacterial small RNA-mediated regulation of host behavior and its transgenerational inheritance in C. elegans' natural environment, and begins to define shared molecular features of bacterial small RNAs that produce transgenerationally inherited effects.