| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2040332 | Cell Reports | 2014 | 8 Pages |
•EIIAGlc is crucial for Salmonella virulence•EIIAGlc virulence function is independent of its well-studied metabolic roles•EIIAGlc is required for virulence factor secretion through TTSS-2•A peculiar EIIAGlc interaction surface is required for TTSS-2 activation
SummaryThe 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.
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