Engineered human antibodies for the opsonization and killing of Staphylococcus aureus

Significance Staphylococcus aureus invariably acquires resistance mechanisms against new antibiotics. The persistent colonization with S. aureus is the key risk factor for invasive disease and a driver for the evolution of antibiotic resistant isolates. Anti- S. aureus antibodies that could promote decolonization, prevent infection, or treat disease would alleviate the selection for drug resistance. The successful development of such antibodies is complicated by Staphylococcal protein A (SpA) in the envelope of S. aureus . SpA captures immunoglobulins via their constant region, preventing antibodies from initiating anti-staphylococcal activities. Here, we demonstrate that therapeutic anti- S. aureus antibodies can be engineered to avoid sequestration by SpA. Such antibodies display extended half-lives and improve bacterial uptake and killing by immune cells.