RT Journal Article SR Electronic T1 Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.15.452486 DO 10.1101/2021.07.15.452486 A1 Sean W. Wallace A1 Malcolm C. Lizzappi A1 Hong Hur A1 Yupu Liang A1 Shai Shaham YR 2021 UL http://biorxiv.org/content/early/2021/07/15/2021.07.15.452486.abstract AB 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 (NHR) NHR-45 and NHR-156 are key 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 NHR gene expansion/diversification underlies adaptation to microbial environments.Competing Interest StatementThe authors have declared no competing interest.