A natural bacterial pathogen ofC. elegansuses a small RNA to induce transgenerational inheritance of learned avoidance

Abstract

A small RNA from a clinical isolate ofPseudomonas aeruginosa, PA14, induces learned avoidance and its transgenerational inheritance inC. elegans. However, it is not known if small RNAs from bacteria found inC. elegans′natural habitat can regulate host behavior and produce heritable behavioral effects. Here we found that GRb0427, a pathogenicPseudomonas vranovensisstrain isolated from theC. elegansmicrobiota, 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 ofC. elegans, JU1580, providing further support that such mechanisms of learning and inheritance exist in the wild. A small RNA, Pv1, matches the sequence ofC. 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 inC. 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.

P. aeruginosacontrols bothC. elegansattraction and pathogenesis by regulating nitrogen assimilation

“…The fact that untrained C. elegans prefer PA14 suggests that in the short term, the need to find nutrients is prioritized over the risk of encountering a pathogen. However, C. elegans have also evolved mechanisms to avoid harmful bacteria in future generations after ingesting them 10,12,26,38 .…”

“…The fact that untrained C. elegans prefer PA14 suggests that in the short term, the need to find nutrients is prioritized over the risk of encountering a pathogen. However, C. elegans have also evolved mechanisms to avoid harmful bacteria in future generations after ingesting them 10,12,26,38 . In this manner, C. elegans may use chemotaxis as a simple form of an adaptive immune system that specifically learns to avoid harmful pathogens only once they are encountered.…”