SUMMARY
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.