Role of rsbU and staphyloxanthin in phagocytosis and intracellular growth of Staphylococcus aureus in human macrophages and endothelial cells.

In Staphylococcus aureus, rsbU down-regulates agr and stimulates production of staphyloxanthin (STX), an antioxidant that may contribute to intracellular survival after phagocytosis. Using isogenic rsbU(-) and rsbU(+) strains, we show that rsbU causes increased internalization and intracellular growth in both THP-1 macrophages and human umbilical vein endothelial cells (more so for the latter) without change in subcellular localization and that inhibition of STX biosynthesis markedly reduces intracellular growth of the rsbU(+) strain (and of clinical isolates, including USA300; tested with macrophages only) without affecting internalization. Thus, rsbU is important for uptake and for STX biosynthesis and is critical for intracellular multiplication of S. aureus.