Identification of Staphylococcus aureus Factors Required for Pathogenicity and Growth in Human Blood.

is a human commensal but also has devastating potential as an opportunistic pathogen. bacteremia is often associated with an adverse outcome. To identify potential targets for novel control approaches, we have identified components that are required for growth in human blood. An ordered transposon mutant library was screened, and 9 genes involved specifically in hemolysis or growth on human blood agar were identified by comparing the mutants to the parental strain. Three genes (, , and ) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The growth defect was specific to the red blood cell component of human blood, showing no difference from the parental strain in growth in human serum, human plasma, or sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the ThyA enzyme and increased demand for pyrimidines in human blood. Our work highlights and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulfonamide antibiotics.