Perturbed sulfur homeostasis allows C. elegans to escape growth retardation on Actinobacteria from its natural microbiome

The rate at which organisms grow is influenced by their biotic environment. The nematode Caenorhabditis elegans grows slower in the presence of Actinobacteria, but it is unknown why. Here, we show how perturbed levels of hydrogen sulfide and cysteine modulate the growth rate of C. elegans on Actinobacteria. Using an unbiased forward genetic screen of C. elegans we discovered alleles of the conserved cystathionine gamma-lyase (cth-2/CTH) that improved animal growth rate on Actinobacteria. Conversely, null alleles of cth-2 cause developmental arrest of animals grown on Actinobacteria, which can be rescued by exogenous H2S. We also discovered a leucine rich repeat gene that regulates cysteine and H2S production, lrr-2/LRRC58. A wild isolate of C. elegans that naturally grows well on Actinobacteria has a mutant allele of lrr-2, suggesting this sulfur metabolism pathway is important for the regulation of animal growth rate in its natural ecological context. We propose a model in which wild-type worms use sulfurous compounds to promote growth of their favored bacterial food sources by inhibiting Actinobacteria growth. This strategy becomes a liability when Actinobacteria are the sole food source but can be bypassed by mutations in sulfur metabolism. This study reveals how the homeostasis of sulfurous compounds controls the growth rate of animals in an ecological context.