biostudies-literatureEl Qaidi SNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSARC Discovery Project GrantNational Institute of General Medical SciencesNIGMS NIH HHSAustralian Research Council Future Fellowship5293https://www.ebi.ac.uk/biostudies/studies/S-EPMC8964723biostudies-literatureUnknown12(1)The Salmonella enterica SseK1 protein is a type three secretion system effector that glycosylates host proteins during infection on specific arginine residues with N-acetyl glucosamine (GlcNAc). SseK1 also Arg-glycosylates endogenous bacterial proteins and we thus hypothesized that SseK1 activities might be integrated with regulating the intrabacterial abundance of UPD-GlcNAc, the sugar-nucleotide donor used by this effector. After searching for new SseK1 substrates, we found that SseK1 glycosylates arginine residues in the dual repressor-activator protein NagC, leading to increased DNA-binding affinity and enhanced expression of the NagC-regulated genes glmU and glmS. SseK1 also glycosylates arginine residues in GlmR, a protein that enhances GlmS activity. This Arg-glycosylation improves Scientific reportsArginine glycosylation regulates UDP-GlcNAc biosynthesis in Salmonella enterica.PMC8964723P20GM130448R21 AI168453FT200100270AI127973DP210100362Scott NEHays MPHardwidge PREl Qaidi SfalseArginine glycosylation regulates UDP-GlcNAc biosynthesis in Salmonella enterica.The Salmonella enterica SseK1 protein is a type three secretion system effector that glycosylates host proteins during infection on specific arginine residues with N-acetyl glucosamine (GlcNAc). SseK1 also Arg-glycosylates endogenous bacterial proteins and we thus hypothesized that SseK1 activities might be integrated with regulating the intrabacterial abundance of UPD-GlcNAc, the sugar-nucleotide donor used by this effector. After searching for new SseK1 substrates, we found that SseK1 glycosylates arginine residues in the dual repressor-activator protein NagC, leading to increased DNA-binding affinity and enhanced expression of the NagC-regulated genes glmU and glmS. SseK1 also glycosylates arginine residues in GlmR, a protein that enhances GlmS activity. This Arg-glycosylation improves 2022-01-01T00:00:00Z2022 Mar2025-05-29T19:46:52.587Z2025-04-05T07:15:35.989ZS-EPMC89647233535194010.1038/s41598-022-09276-9