C. elegans intergenerational and transgenerational responses to P. aeruginosa

Abstract

Caenorhabditis elegans are found in the wild all over the world where they survive by eating the various bacterial species in their environment. 21% of the bacteria in the worm’s natural environment are from the genus Pseudomonae including the gram-negative pathogen Pseudomonas aeruginosa (PA14). Prolonged exposure to PA14 results in death and therefore extinction of the population. It has been reported that experiences trigger small RNA based-responses in C. elegans. Here, we identify a novel intergenerational and transgenerational response to P. aeruginosa. When C. elegans encounters PA14 worms become sick and eventually will die if they cannot escape. We found that when worms are exposed to PA14 during the reproductive period, progeny that are laid and hatch on PA14 have two development fates: (1) pre-reproductive arrest (L4 arrest), or (2) post-reproductive diapause (adult reproductive diapause, ARD). This intergenerational-developmental effect is advantageous because the L4-arrested state prolongs the survival of C. elegans undergoing chronic PA14 infection, while the ARD state allows for efficient reproduction when worms locate more nutritious food. In addition to becoming sick during P. aeruginosa exposure worms can learn to avoid PA14 if given the choice between PA14 and its normal laboratory food. We discovered that in addition to learning to avoid PA14, mothers can pass this information on to their progeny for four generations before resuming naïve attraction in the fifth. This mechanism requires the piRNA machinery, the COMPASS complex of epigenetic regulators and the ASI sensory neuron. We then discovered that worms can “read” bacterial small RNAs using the canonical RNAi pathway in the intestine, piRNA signaling in the germline, and transcriptional changes in the ASI neuron. The components required for avoidance behavior in the mother are also required in the progeny suggesting we have identified a novel inter-tissue signaling mechanism that conveys bacterial identity in order to promote survival transgenerationally. Finally, we found that the Ty3/Gypsy retrotransposon Cer1 forms viral-like particles in the germline and is required for survival on PA14, for transmitting the avoidance signal from the germline to neurons, and for transgenerational inheritance of pathogen avoidance. Furthermore, we found that transgenerational pathogen avoidance can be horizontally transmitted and transgenerationally inherited in naïve worms. These effects are conserved in wild C. elegans isolates suggesting that worms have co-opted a potentially dangerous retrotransposon to help them avoid pathogens and promote transgenerational survival.