How does complement activation kill pathogenic bacteria?

Our immune system uses molecular machines that punch holes in bacteria to fight infection. These holes are made by the membrane attack complex (MAC), a protein-based pore that pierces the protective barrier of bacterial cells. Although MAC pores perforate the surface of these bacteria, it is unknown how the inner membrane is breached to cause cell death. Here we aim to understand the key factors that render bacteria susceptible to MAC. We use novel models of bacterial envelopes for experiments that link structural information with dynamics of protein interactions. We will investigate where MAC is in the context of the bacterial membrane and assess how this results in cell killing. We will also determine how local assembly on the cell surface contributes to MAC activity. This is important because pores that don't assemble correctly can't kill cells. Together, our experiments will help explain how MAC protects us from pathogenic bacteria.