Efflux Transporter Of Siderophore Staphyloferrin A In Staphylococcus Aureus Contributes To Bacterial Fitness In Abscesses And Epithelial Cells

The siderophores staphyloferrin A (SA) and staphyloferrin B (SB) of Staphylococcus aureus are essential for iron acquisition in the iron-restricted environment of the host, such as in subcutaneous abscesses. SA and SB are secreted by SfaA and SbnD transporters, respectively. To assess the further function of SfaA and SbnD in S. aureus fitness, we tested its effect on murine abscess models and intracellular replication in epithelial cells. Bacterial fitness in abscesses and in epithelial cells was studied, by comparing the parental strains RN6390 and MW2 and their Delta sfaA and Delta sbnD mutants using competition assays in a murine abscess model and invasion and replication assays with human lung adenocarcinoma cell line A549. In the murine abscess model using equal inocula of a Delta sfaA or Delta sbnD mutant and the wild-type RN6390 strain, the Delta sfaA mutant exhibited growth defects of 2.2-fold. Additionally, replication of the Delta sfaA mutant within A549 cells was decreased 3.0-fold. In complementation experiments, the Delta sfaA mutant carrying plasmid-borne Delta sfaA restored the growth fitness in abscesses and epithelial cells. The Delta sbnD mutant, in contrast, showed no growth defect in either abscesses or epithelial cells. Our findings demonstrate that the efflux transporter of the siderophore SA contributes to the ability of S. aureus to replicate in abscesses and epithelial cells. Furthermore, fitness of S. aureus in these sites of replication is not compromised by the absence of transporter SbnD.