The present study investigated the effects of iron, iron chelators, and mutations of tonB or iroN fepA genes on the growth and virulence of Salmonella Typhimurium . Results indicated that organic iron (ferric citrate and ferrous-l-ascorbate) supported better growth of Salmonella compared to inorganic iron. Among tested chelators, 2,2'-bipyridyl at 500 μM showed the highest inhibition of Salmonella growth with 5 μM ferrous sulfate. Deletion of genes ( tonB - and iroN - fepA - ) in the iron uptake system attenuated Salmonella invasion of Caco-2 cells and its ability to damage the epithelial monolayer. The expression of all tested host genes in Caco-2 was not affected under the iron-poor condition. However, claudin 3, tight junction protein 1, tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) were altered under the iron-rich condition depending on individual mutations. In Caenorhabditis elegans , a significant down-regulation of ferritin 1 expression was observed when the nematode was infected by the wild-type (WT) strain., Competing Interests: The authors declare no competing financial interest.