Understanding host restriction following bacterial phagosome rupture

Immune cells engulf and kill microorganisms inside phagosomes. However, some microorganisms avoid their destruction by damaging the phagosomal membrane. This activates autophagy, which can sometimes clear the infection, but might also be irrelevant or beneficial for bacterial survival. Potentially providing a restriction alternative is the ESCRT machinery, which has been proposed to repair membrane disruptions. I want to investigate the interplay between ESCRTs and autophagy during Staphylococcus aureus infection. Advanced optical microscopy will enable me to follow both machineries in high resolution and may help to understand factors triggering each pathway and their contribution to intracellular bacterial killing. It will also be important to identify bacterial factors that can modify autophagy and / or ESCRT recruitment. Moreover, I aim to discover unknown host regulators of autophagy, ESCRT and cellular immunity that enhance bacterial restriction and might offer potential targets for new therapeutic regimes for infection control.