Pseudomonas fluorescens 15small RNA Pfs1 mediates transgenerational epigenetic inheritance of pathogen avoidance inC. elegansthrough the Ephrin receptor VAB-1

Abstract

AbstractC. elegansare exposed to a variety of pathogenic and non-pathogenic bacteria species in their natural environment. Correspondingly,C. eleganshas evolved an ability to discern between nutritive and infectious bacterial food sources. Here we show thatC. eleganscan learn to avoid the pathogenic bacteriaPseudomonas fluorescens 15(PF15), and that this learned avoidance behavior is passed on to progeny for four generations, as we previously demonstrated forPseudomonas aeruginosa(PA14) andPseudomonas vranovensis, using similar mechanisms, including the involvement of both the TGF-β ligand DAF-7 andCer1retrotransposon-encoded virus-like particles. PF15 small RNAs are both necessary and sufficient to induce this transgenerational avoidance behavior. Unlike PA14 orP. vranovensis, PF15 does not use P11, Pv1, or a small RNA withmaco-1homology for this avoidance; instead, an unrelated PF15 small RNA, Pfs1, that targets theC. elegans vab-1Ephrin receptor gene is necessary and sufficient for learned avoidance, suggesting the evolution of yet another bacterial sRNA/C. elegansgene target pair involved in transgenerational inheritance of pathogen avoidance. As VAB-2 Ephrin receptor ligand and MACO-1 knockdown also induce PF15 avoidance, we have begun to understand the genetic pathway involved in small RNA targeted pathogenic avoidance. Moreover, these data show that axon guidance pathway genes (VAB-1 and VAB-2) have previously unknown adult roles in regulating neuronal function.C. elegansmay have evolved multiple bacterial specificity-encoded small RNA-dependent mechanisms to avoid different pathogenic bacteria species, thereby providing progeny with a survival advantage in a dynamic environment.