<i>C. elegans</i> transgenerational avoidance of <i>P. fluorescens</i> is mediated by the Pfs1 sRNA and <i>vab-1</i>

In its natural habitat, <i>Caenorhabditis elegans</i> must distinguish friend from foe. <i>Pseudomonas</i> are abundant in the worm's environment and can be nutritious or pathogenic. Previously, we found that worms learn to avoid <i>Pseudomonas aeruginosa</i> and <i>Pseudomonas vranovensis</i> through a small RNA (sRNA)-mediated pathway targeting the <i>C. elegans</i> gene <i>maco-1</i>, and this behavior is inherited for four generations. Here, we show that <i>C. elegans</i> learns to transgenerationally avoid another pathogenic bacteria <i>Pseudomonas fluorescens</i> 15 (PF15). The PF15 sRNA, Pfs1, targets the <i>VAB-1</i> ephrin receptor through 16 nt of perfect match, suggesting the evolution of a distinct bacterial sRNA/<i>C. elegans</i> gene target pair. Knockdown of both <i>maco-1 and vab-1</i> induce PF15 avoidance, and <i>vab-1</i> loss reduces <i>maco-1</i> expression, placing both genes in the sRNA-targeted pathogenic avoidance pathway. Thus, multiple genes in this avoidance pathway can act as targets for bacterial sRNAs, expanding the possibilities for evolution of trans-kingdom regulation of <i>C. elegans</i> behavior.