Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection

Abstract

Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. Here we report that the soil bacteria Pseudomonas vranovensis is a natural pathogen of the nematode Caenorhabditis elegans and that parental exposure of animals to P. vranovensis promotes offspring resistance to infection. Furthermore, we demonstrate a multigenerational enhancement of progeny survival when three consecutive generations of animals are exposed to P. vranovensis. By investigating the mechanisms by which animals heritably adapt to P. vranovensis infection, we found that parental infection by P. vranovensis results in increased expression of the cysteine synthases cysl-1 and cysl-2 and the regulator of hypoxia inducible factor rhy-1 in progeny, and that these three genes are required for adaptation to P. vranovensis. These observations establish a CYSL-1, CYSL-2, and RHY-1 dependent mechanism by which animals heritably adapt to infection.

A parental transcriptional response to microsporidia infection induces inherited immunity in offspring

“…Inherited immunity is a nascent and rapidly growing field of research, with important consequences for our understanding of health and evolution. Multiple studies have now demonstrated that parental exposure to one pathogen can protect offspring against subsequent exposure to the same pathogen 1,13,19,43 . Several studies have also shown that parents exposed to a particular stress can produce progeny that are protected against the same stress, and that abiotic stress can provide transgenerational resistance to pathogenic infection 5,6,[44][45][46] .…”

“…We found that the offspring of N. parisii infected mutants still became protected against infection ( fig. S8, A to D) 19,36 . In addition, we found that the master immune regulator PMK-1 was not required for the induction of inherited immunity, consistent with this pathway not being involved in immunity to N. parisii ( fig.…”

Nongenetic inheritance and multigenerational plasticity in the nematode C. elegans

“…In addition to inducing avoidance behavior and dauer formation in descendants, exposure to bacterial pathogens can induce heritable resistance to infection. Non-lethal adult exposure to the novel C. elegans pathogen Pseudomonas vranovensis induces resistance to the same pathogen in first-generation progeny, an intergenerational effect, with a substantial effect size ( Burton et al, 2020 ). Exposure for three consecutive generations triggers resistance for two subsequent generations, suggesting epigenetic inheritance but falling one generation short of the three-generation gold standard.…”

What can a worm learn in a bacteria-rich habitat?

“…In addition to food-seeking related behavior, exposing the worms to pathogenic bacteria generates intergenerational effects on other physiological traits critical for survival. For example, exposure to Pseudomonas vranovensis, another bacterium pathogenic to C. elegans, generates multigenerational effects and enhances immune resistance to the pathogen in the offspring (Burton et al, 2019). Meanwhile, exposure to certain pathogenic bacteria for two consecutive generations induces formation of dauers, a dormant development stage that is highly resistant to environmental stresses (Palominos et al, 2017).…”