Salmonella species can gain access into nonphagocytic cells,where the bacterium proliferates in a unique membrane-bounded compartment.In order to reveal bacterial adaptations to their intracellular niche,here we conducted the first comprehensive proteomic survey of Salmonella isolated from infected epithelial cells.Among ~3,300 identified bacterial proteins, we found that about 100 proteins weresignificantly altered at the onset of Salmonella intracellular replication. Inaddition to substantially increased iron-uptake capacities, bacterial high-affinitymanganese and zinc transporters were also upregulated, suggesting an overalllimitation of metal ions in host epithelial cells. We also found that Salmonellainduced multiple phosphate utilization pathways. Furthermore, our data suggestedupregulation of the two-component PhoPQ system as well as of many downstream virulencefactors under its regulation. Our survey also revealed that intracellular Salmonellahas increased needs for certain amino acids and biotin. In contrast, Salmonelladownregulated glycerol and maltose utilization as well as chemotaxis pathways.
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