Defeat Staphylococcus aureus by targeting multiple iron acquisition systems

Staphylococcus aureus is a bacterial pathogen causing a broad spectrum of human diseases. S. aureus has reached an alarming high level of antibiotic resistance, leaving few viable therapeutic options to clinicians, and urgently calling for novel anti-Staphylococcus treatments. Given the crucial role of iron in bacterial physiology and pathogenicity, iron uptake and metabolism have been evaluated as possible drug targets. During infection, S. aureus acquires iron from heme, the preferred iron source, via the IsdB and IsdH hemophores, and other proteins (also belonging to the Iron-regulated surface determinant Isd-system) able to deliver iron to the cytoplasm. Moreover, S. aureus can also acquire iron by producing two siderophores, namely staphyloferrin A (SA) and staphyloferrin B (SB). As part of the ERASE multidisciplinary project (PRIN2020AE3LTA), the aim of this study is to investigate two mechanisms of iron acquisition by S. aureus: heme scavenging by IsdB/IsdH and iron uptake by SB, setting up the conditions to assay possible inhibitors of these processes, hence of S. aureus growth. We have determined suitable growth conditions to investigate the effect of iron starvation in S. aureus, represented by the iron-deplete medium cTMS (Chelex-treated Tris Minimal Succinate), in which high levels of siderophore were produced by S. aureus. Moreover, the addition of Hemoglobin or FeCl3 in cTMS promoted bacterial growth, thus confirming that iron is perceived as a limiting nutrient in this medium. Additionally, an isdB in frame deletion mutant has been successfully generated and its contribution to the growth of S. aureus is currently under investigation.