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

Nicholas O Burton,Alexandra Dallaire,Albert Koulman,Cristian Riccio,Benjamin Jenkins,Jonathan Price,Eric A Miska

doi:10.1038/s41467-020-15555-8

Nicholas O Burton, Alexandra Dallaire + Show 5 more

Open Access

https://doi.org/10.1038/s41467-020-15555-8

Copy DOI

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.

Highlights

Parental exposure to pathogens can prime offspring immunity in diverse organisms
When comparing genes regulated by P. vranovensis to genes regulated by other microbes, we found that C. elegans response to P. vranovensis is most similar to C. elegans response to the pathogen Photorhabdus luminescens[29], with 46 out of 100 genes upregulated in response to both pathogens, and to the pathogen Pseudomonas aeruginosa[30], with 28 of 100 genes upregulated by both pathogens[31]
We found that only 41 genes exhibited a greater than twofold change in expression in embryos from parents exposed to P. aeruginosa when compared to embryos from parents fed E. coli HB101 and of these genes only 29 exhibited altered gene expression in embryos from parents exposed to P. vranovensis (Fig. 3d and Supplementary Data 6)

Summary

Introduction

Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. 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. Parental exposure to high population density was demonstrated to promote an accelerated postnatal growth rate in red squirrels that enhanced offspring survival by allowing them to acquire territories more quickly[2] These findings raise the exciting possibility that parental exposure to environmental stress causing programmed changes in offspring physiology might represent a fundamental and significantly understudied aspect of inheritance with implications for diverse fields of biological and medical sciences. Similar observations of parents priming offspring immunity in response to pathogens have been reported in both plants[15] and invertebrates[11], even though these organisms lack antibodies. We identify that Caenorhabditis elegans can heritably adapt to a natural pathogen, Pseudomonas vranovensis, and that adaptation to P. vranovensis requires the cysteine synthases CYSL-1 and CYSL-2 and the regulator of hypoxia inducible factor RHY-1

Methods

Results

Conclusion