Hydrogen sulfide mediates the interaction between C. elegans and Actinobacteria from its natural microbial environment

Caenorhabditis elegans proliferates poorly in the presence of abundant Actinobacteria from its natural ecology, but it is unknown why. Here, we show how perturbed levels of hydrogen sulfide modulate the growth rate of both C. elegans and Actinobacteria. From a forward genetic selection, we find C. elegans mutants with faster growth on an Actinobacteria Microbacterium species and mutant alleles of conserved cystathionine gamma-lyase (cth-2/CTH) that improve growth rate. Conversely, null alleles of cth-2 cause developmental arrest of animals grown on Actinobacteria, but not on Proteobacteria, which can be rescued by exogenous H₂S. We also find mutations in a leucine-rich-repeat gene that regulates cysteine and H₂S production, lrr-2/LRRC58. We place lrr-2 in the animal sulfur metabolism pathway by demonstrating its role in post-translationally regulating levels of cysteine dioxygenase (cdo-1/CDO1). Exogenously supplied H₂S inhibits the growth of Actinobacteria but not Proteobacteria. Thus, we conclude that the C. elegans-Actinobacteria interaction is mediated by H₂S.