Enzyme IIA(Ntr) Regulates Salmonella Invasion Via 1,2-Propanediol And Propionate Catabolism

Many Proteobacteria possess a nitrogen-metabolic phosphotransferase system (PTS(Ntr)) consisting of EI(Ntr), NPr, and EIIA(Ntr) (encoded by ptsP, ptsO, and ptsN, respectively). The PTS(Ntr) plays diverse regulatory roles, but the substrate phosphorylated by EIIA(Ntr) and its primary functions have not yet been identified. To comprehensively understand the roles of PTS(Ntr) in Salmonella Typhimurium, we compared the whole transcriptomes of wild-type and a ΔptsN mutant. Genome-wide RNA sequencing revealed that 3.5% of the annotated genes were up- or down-regulated by three-fold or more in the absence of EIIA(Ntr). The ΔptsN mutant significantly down-regulated the expression of genes involved in vitamin B(12) synthesis, 1,2-propanediol utilization, and propionate catabolism. Moreover, the invasiveness of the ΔptsN mutant increased about 5-fold when 1,2-propanediol or propionate was added, which was attributable to the increased stability of HilD, the transcriptional regulator of Salmonella pathogenicity island-1. Interestingly, an abundance of 1,2-propanediol or propionate promoted the production of EIIA(Ntr), suggesting the possibility of a positive feedback loop between EIIA(Ntr) and two catabolic pathways. These results demonstrate that EIIA(Ntr) is a key factor for the utilization of 1,2-propanediol and propionate as carbon and energy sources, and thereby modulates the invasiveness of Salmonella via 1,2-propanediol or propionate catabolism.