A natural bacterial pathogen of C. elegans uses a small RNA to induce transgenerational inheritance of learned avoidance

Titas Sengupta, Jonathan S. Ange, Rachel Kaletsky, Rebecca S. Moore, Renee J. Seto, Jacob Marogi, Cameron Myhrvold, Zemer Gitai, Coleen T. Murphy

Research output: Contribution to journalArticlepeer-review


C. elegans can learn to avoid pathogenic bacteria through several mechanisms, including bacterial small RNA-induced learned avoidance behavior, which can be inherited transgenerationally. Previously, we discovered that a small RNA from a clinical isolate of Pseudomonas aeruginosa, PA14, induces learned avoidance and transgenerational inheritance of that avoidance in C. elegans. Pseudomonas aeruginosa is an important human pathogen, and there are other Pseudomonads in C. elegans' natural habitat, but it is unclear whether C. elegans ever encounters PA14-like bacteria in the wild. Thus, it is not known if small RNAs from bacteria found in C. elegans' natural habitat can also regulate host behavior and produce heritable behavioral effects. Here we screened a set of wild habitat bacteria, and found that a pathogenic Pseudomonas vranovensis strain isolated from the C. elegans microbiota, GRb0427, regulates 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 bacterially-produced small RNAs, which induce avoidance and transgenerational inheritance, providing further support that such mechanisms of learning and inheritance exist in the wild. We identified Pv1, a small RNA expressed in P. vranovensis, that has a 16-nucleotide match to an exon of the C. elegans gene maco-1. Pv1 is both necessary and sufficient to induce learned avoidance of Grb0427. However, Pv1 also results in avoidance of a beneficial microbiome strain, P. mendocina. Our findings suggest that bacterial small RNA-mediated regulation of host behavior and its transgenerational inheritance may be functional in C. elegans' natural environment, and that this potentially maladaptive response may favor reversal of the transgenerational memory after a few generations. Our data also suggest that different bacterial small RNA-mediated regulation systems evolved independently, but define shared molecular features of bacterial small RNAs that produce transgenerationally-inherited effects.

Original languageEnglish (US)
Article numbere1011178
JournalPLoS genetics
Issue number3
StatePublished - Mar 28 2024

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Cancer Research


Dive into the research topics of 'A natural bacterial pathogen of C. elegans uses a small RNA to induce transgenerational inheritance of learned avoidance'. Together they form a unique fingerprint.

Cite this