A Nitrogen Metabolic Enzyme Provides Salmonella Fitness Advantage by Promoting Utilization of Microbiota-Derived...

Microbes support their growth in vertebrate hosts by exploiting a large variety of dietary components as nutrients, which determines the composition of gut microbiota. A pathogen Salmonella expands by utilizing 1,2-propanediol, a microbiota-fermented product, during mucosal inflammation. However, it remains largely unknown how the pathogen decides which nutrient to consume from the complex mixture in the gut. Here, we show that Salmonella enterica serovar Typhimurium utilizes 1,2-propanediol by EIIA^Ntr (a nitrogen-metabolic PTS component implicated in virulence)-mediated regulation of the pdu operon, thereby expanding in the murine intestine. Propionyl-CoA, a metabolic intermediate produced by 1,2-propanediol catabolism, elevates EIIA^Ntr protein amounts, entailing positive feedback, thereby boosting the 1,2-propanediol-utilization process. EIIA^Ntr promotes pdu expression by enhancing glutathione synthesis. CRP (cAMP receptor protein) induces pdu genes by increasing EIIA^Ntr expression in response to glucose availability. Notably, EIIA^Ntr-mediated 1,2-propanediol-utilization conferred a growth benefit even under high glucose conditions which reduces CRP activity. The EIIA^Ntr-mediated activation is likely conserved in pathogenic enterobacteria including Escherichia coli. Collectively, our findings suggest that Salmonella promotes its fitness by precisely modulating the utilization system for microbiota-derived carbon source. They also suggest that Salmonella may integrate signals, processed via EIIA^Ntr, into its metabolic program as well as virulence circuit.