Multiple drug resistance to antibiotics is a major public health problem. Many mechanisms may be involved in such resistance. Increasing data have shown that Staphylococcus aureus can invade different types of nonphagocytic cells, which, in turn, may contribute to evasion of the toxicity of certain antibiotics. The fibronectin-binding proteins are required for S. aureus to adhere to and internalize into the host cells. We have shown that a twocomponent signal transduction system, SaeRS, is essential for bacterial adhesion and invasion of the epithelial cells.