Molecular decision points underlying the systemic spreading of Staphylococcus aureus
Prof. Dr. Eva Medina & Dr. Martin Fraunholz
Staphylococcus aureus is an invasive human pathogen that can disseminate via the bloodstream from a local site of infection and cause progressive, chronic, or recurrent infections in distant organs. After hematogenous dissemination, the liver constitutes the first line of defence by filtering S. aureus from the circulation via liver-resident Kupffer cells. When Kupffer cells and blood stream phagocytes fail to completely eliminate the pathogen, the phagocytes harbouring viable bacteria promote dissemination of infection to secondary organs, such as kidneys and bones. The host responds to bacterial seeding and proliferation in these organs by recruiting immune cells that accumulate at the nidus of infection to wall off the pathogen, giving rise to abscesses. The failure of abscesses to contain S. aureus can lead to infection recurrence. Our hypothesis is that the outcome of S. aureus systemic infection relies on molecular decision points that control the capacity of phagocytes to clear S. aureus from the bloodstream, and thereby influence bacterial spreading and infection of secondary organs. The objective of this project is to identify these molecular decision points since they represent novel host targets for therapeutic intervention.