Staphyloccous aureus is a major human pathogen capable of causing a wide spectrum of infections ranging from superficial wound infections to life-threatening endocarditis and toxic shock syndrome. Essential for S. aureus virulence is a large number of cell-surface-associated proteins and secreted proteins. Results from our group have shown that the ClpXP proteolytic complex and the ClpX chaperone play central roles in regulating expression of many of these factors (2;3). By using DNA microarrays to compare transcription of strain 8325-4 (wt) and the isogenic ¿clpX strain during the transition phase we show here that almost 400 genes (15%) are influenced by the clpX deletion. Furthermore, ClpX not only regulates many virulence factors, but rather serves as a global regulator of central functions for S. aureus lifestyle and pathogenicity.