Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum

Animals encounter microorganisms in their habitats, adapting physiology and behavior accordingly. The nematode Caenorhabditis elegans is found in microbe-rich environments; however, its responses to fungi are not extensively studied. Here, we describe interactions of C. elegans and Penicillium brevicompactum, an ecologically relevant mold. Transcriptome studies reveal that co-culture upregulates stress response genes, including xenobiotic-metabolizing enzymes (XMEs), in C. elegans intestine and AMsh glial cells. The nuclear hormone receptors (NHRs) NHR-45 and NHR-156 are induction regulators, and mutants that cannot induce XMEs in the intestine when exposed to P. brevicompactum experience mitochondrial stress and exhibit developmental defects. Different C. elegans wild isolates harbor sequence polymorphisms in nhr-156, resulting in phenotypic diversity in AMsh glia responses to microbe exposure. We propose that P. brevicompactum mitochondria-targeting mycotoxins are deactivated by intestinal detoxification, allowing tolerance to moldy environments. Our studies support the idea that C. elegans NHRs may be regulated by environmental cues. [Display omitted] •The mold P. brevicompactum induces XME expression in C. elegans gut and glia•P. brevicompactum-dependent XME induction is regulated by nhr-45 and nhr-156•Failure to induce XMEs in the intestine results in mitochondrial stress and toxicity•Natural variations in nhr-156 result in phenotypic diversity in the glial response C. elegans inhabits microbe-rich environments, and there is currently great interest in understanding how they interact with the microbes they encounter in the wild. Wallace et al. describe a transcriptional response that protects C. elegans from mitochondrial toxicity when exposed to the fungal mold Penicillium brevicompactum.