The central metabolism regulator EIIAGlc switches Salmonella from growth arrest to acute virulence through activation of virulence factor secretion.
The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2) involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism.
Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland; Synthetic Biology, UMR7242, ESBS, University of Strasbourg, 67412 Illkirch, France.
Alain
A
Mazé
Proteomics Core Facility, Biozentrum, University of Basel, 4056 Basel, Switzerland.
Timo
T
Glatter
Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address: dirk.bumann@unibas.ch.
Dirk
D
Bumann
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D004843:Epistasis, Genetic; D051379:Mice; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D037521:Virulence Factors; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D000262:Adenylyl Cyclases