The application of label free quantitation (LFQ) to the profiling of secreted proteomes is a powerful tool in the deciphering of these mechanisms and the determination of the severity of infection with different strains. Our study consists of three distinct, but interconnected experiments resulting in an extensive data set for the identification of antigens. First we explore the changes in virulence factor secretion when regulators are mutated, then compare these effects in two different growth conditions. We further explore the effects of nutrient accessibility by profiling the secreted proteomes of S. aureus at different points in the colony growth curve in both a rich and minimal media. Lastly, the secreted proteins from a selection of twelve strain types representing 5 colony complexes are quantified and compared to the cytotoxicity of the strains. Biological triplicates were used for mutant and growth curve studies.