Staphylococcus aureus is the cause numerous deadly infectious diseases and has the capacity to infect every tissue in the human body. Its virulence depends on a complex network of known protein virulence factors and small molecules that assist in infectious cycles. Because of the relatively recent finding that nonribosomal peptides from other pathogens act as important virulence factors we have applied genome mining strategies to identify nonribosomal peptides made by methicillin-resistant Staphylococcus aureus. Within S. aureus genomes is a cryptic nonribosomal peptide synthetase (NRPS) gene cluster whose genes were shown previously to be upregulated by cell-wall active antibiotics, under the control of the S. aureus accessory gene regulator and whose expression coincides with known virulence factors. Using molecular principles of nonribosomal peptide assembly member of the Magarvey Lab derived structure predictions of the encoded nonribosomal peptides. Mass-directed and structure-guided natural product isolation strategies led to the isolation of the NRPS-encoded cyclic peptides (named staphylomycin A and B). Using a series of NMR-experiments and X-ray structure analysis we have solved the structure of the staphylomycins and show the presents of a unique pyrazinone core. Using genetic and small molecule analysis these nonribosomal peptides were shown to be produced by all virulent human staphylococcal strains, including every strain of Canadian Methicillin Resistant S. aureus. In this poster, I described the isolation, characterization, biosynthesis and actions of the staphylomycins from MRSA strains.