Umbau der Wirtslipidlandschaft durch Staphylococcus aureus und Auswirkungen auf Infekton und Entzündung.

01.01.2026 bis 31.12.2028

Lipids play multiple roles at the host – pathogen interface, including signaling to activate immune responses or binding to bacteria to inhibit their growth. Bacteria colonizing mucosal surfaces and the skin have unsurprisingly evolved several strategies to manipulate host-derived lipids. These strategies are not yet fully understood and disentangling them may open new avenues to combat multidrug-resistant bacteria. In this research proposal, we aim to dissect the molecular determinants and mechanisms of S. aureus-mediated production of lipokines. Furthermore, we will leverage a murine infection model to investigate bacteria-elicited synthesis of lipokines in vivo. In this in vivo model, we will also explore the extent to which lipokines alleviate inflammation to enable the proliferation of S. aureus. For a better mechanistic understanding of the signaling cascades triggered by lipokines, we will analyze cytokine release and/or activation of G Protein-coupled receptors by established cell lines and primary cells from mice or healthy volunteers upon incubation with S. aureus or its exoproducts. The roles of these lipid mediators in the intracellular survival of S. aureus will also be investigated. Taken together, the proposed experiments are tailored to uncover and characterize underappreciated lipid mediators used by S. aureus – and most likely other bacterial members of the microbiome – to blunt innate immune recognition of their otherwise highly proinflammatory microbial associated molecular patterns.