In this study, we add the neutrophil cytoplasmic protein CP to the list of the host factors exploited by S. aureus. CP is important to restrict growth through metal chelation in abscesses; however, our data also suggest that, during high dose systemic infections, its antimicrobial activity increases the activity of the SaeRS TCS and its proinflammatory properties can lead to higher mortality of the host, shedding new light on the evolutionary tug-of-war between microbial pathogens and host. Here, PROS1 is linked to abscess.