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

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