Widespread Bacterial Utilization of Guanidine as Nitrogen Source

Abstract

Guanidine is sensed by at least four different classes of riboswitches that are widespread in bacteria. However, only very few insights into physiological roles of guanidine exist. Genes predominantly regulated by guanidine riboswitches are Gdx transporters exporting the compound from the bacterial cell. In addition, urea/guanidine carboxylases and associated hydrolases and ABC transporters are often found combined in guanidine‐inducible operons. We noted that the associated ABC transporters are configured to function as importers, challenging the current view that riboswitches solely control the detoxification of guanidine in bacteria. We demonstrate that the carboxylase pathway enables utilization of guanidine as sole nitrogen source. We isolated three enterobacteria (Raultella terrigena,Klebsiella michiganensis, and Erwinia rhapontici) that utilize guanidine efficiently as N‐source. Proteome analyses show that the expression of a carboxylase, associated hydrolases and transport genes is strongly induced by guanidine. Finding two urea/guanidine carboxylase enzymes in E. rhapontici, we demonstrate that the riboswitch‐controlled carboxylase displays specificity towards guanidine whereas the other enzyme prefers urea. We characterize the distribution of riboswitch‐associated carboxylases and Gdx exporters in bacterial habitats by analysing available metagenome data. The findings represent a paradigm shift from riboswitch‐controlled detoxification of guanidine to the uptake and assimilation of this enigmatic nitrogen‐rich compound.