Biological organisms require iron for optimal metabolism. Intracellular pathogens also must secure iron especially during infection of animal hosts expressing NRAMP(natural resistance-associated macrophage protein), a transporter protein sequestering metal ions from pathogens. This study shows that extracytoplasmic function sigma factor σE is required for Salmonella virulence in NRAMP1-expressing mice, and further shows that iron deprivation turns on σE expression of Salmonella. The virulence of σE -deficient Salmonella is completely attenuated in C3H/HeN mice while wild type Salmonella kills all mice. Addition of an iron-chelator DTPA(Diethylene triamine pentaacetic acid) to culture media induces σE expression of Salmonella, but iron supplementation abrogates this induction. These findings suggest that iron limitation in host macrophages can trigger σE -dependent virulence system of Salmonella that may include bacterial iron homeostasis.