Yoo W, Choi J, Park B, Byndloss MX, Ryu S. A Nitrogen Metabolic Enzyme Provides Fitness Advantage by Promoting Utilization of Microbiota-Derived Carbon Source. ACS infectious diseases. 2021 Dec 14;7(7). 1208-1220. PMID: 33853321 [PubMed] PMCID: PMC8603301 NIHMSID: NIHMS1748056.
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 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 serovar Typhimurium utilizes 1,2-propanediol by EIIA (a nitrogen-metabolic PTS component implicated in virulence)-mediated regulation of the operon, thereby expanding in the murine intestine. Propionyl-CoA, a metabolic intermediate produced by 1,2-propanediol catabolism, elevates EIIA protein amounts, entailing positive feedback, thereby boosting the 1,2-propanediol-utilization process. EIIA promotes expression by enhancing glutathione synthesis. CRP (cAMP receptor protein) induces genes by increasing EIIA expression in response to glucose availability. Notably, EIIA-mediated 1,2-propanediol-utilization conferred a growth benefit even under high glucose conditions which reduces CRP activity. The EIIA-mediated activation is likely conserved in pathogenic enterobacteria including Collectively, our findings suggest that promotes its fitness by precisely modulating the utilization system for microbiota-derived carbon source. They also suggest that may integrate signals, processed via EIIA, into its metabolic program as well as virulence circuit.