Perturbed sulfur homeostasis allowsC. elegansto escape growth retardation onActinobacteriafrom its natural microbiome

Abstract

SummaryThe rate at which organisms grow is influenced by their biotic environment. The nematodeCaenorhabditis elegansgrows slower in the presence ofActinobacteria, but it is unknown why. Here, we show how perturbed levels of hydrogen sulfide and cysteine modulate the growth rate ofC. elegansonActinobacteria. Using an unbiased forward genetic screen ofC. eleganswe discovered alleles of the conserved cystathionine gamma-lyase (cth-2/CTH)that improved animal growth rate onActinobacteria. Conversely, null alleles ofcth-2cause developmental arrest of animals grown onActinobacteria, 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 ofC. elegansthat naturally grows well onActinobacteriahas a mutant allele oflrr-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 inhibitingActinobacteriagrowth. This strategy becomes a liability whenActinobacteriaare 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.