The pathogen Staphylococcus aureus colonizes the anterior nares of humans and causes invasive infections with high morbidity and mortality. For successful colonization and infection, pathogens need to overcome humoral and cellular immune defenses. Additionally, pathogens need to acquire host-derived nutrients, adhere to extracellular matrix molecules and compete with commensals within their human niche. The focus of our research lies on staphylococcal iron acquisition. Iron is essential for bacterial proliferation and the active limitation of iron within human tissues as well as on mucosal surfaces is an effective immune effector mechanism to inhibit bacterial growth. To overcome iron restriction, S. aureus encodes sophisticated systems to acquire host- derived heme. We show that hemolytic staphylococcal toxins act in a concerted fashion with heme acquisition systems. Additionally, we show that heme acquisition systems of S. aureus are coordinated molecular machineries relying on spatial structuring by membrane microdomains.
Finally, we show that competition for nutritional iron is an important trait within the human nasal microbiome. Nasal commensal species can acquire iron-binding siderophores produced by S. aureus, and can reduce pathogen proliferation in an iron- dependent fashion.
Altogether our data give insight into the relevance of S. aureus iron-acquisition during colonization and infection of the human host.