Human immune protection against invading bacteria critically depends on the action of the complement system. Complement is a large protein network in plasma that labels bacteria for phagocytosis by immune cells and directly kills Gram-negative bacteria via Membrane Attack Complex (MAC) pores. My laboratory aims to unravel molecular mechanisms underlying complement-dependent bacterial killing. Currently it is not understood how MAC perturbs complex cell envelopes of Gram-negative bacteria with two membranes. During this presentation I will discuss our recent data showing that MAC in human serum requires perturbation of both bacterial membranes in order to kill the cell. C5 convertase enzymes, large protein complexes deposited on the bacterial cell surface via antibody or pattern recognition pathways, were found essential for proper insertion of MAC pores into bacterial membranes. Since antibiotic-resistant bacteria form a serious threat for public health, we ultimately aim to translate mechanistic insights of immune dependent bacterial killing into new immune therapies to treat antibiotic-resistant bacteria.