Lysostaphin lysibody leads to effective opsonization and killing of methicillin resistant Staphylococcus aureus in a murine model.

Lysostaphin lysibody leads to effective opsonization and killing of methicillin resistant Staphylococcus aureus in a murine model. Antimicrob Agents Chemother. 2018 Jul 23;: Authors: Raz A, Serrano A, Thaker M, Alston T, Fischetti VA Abstract The cell wall of Gram-positive bacteria contains abundant surface-exposed carbohydrate structures that are highly conserved. While these properties make surface carbohydrates ideal targets for immunotherapy, carbohydrates elicit a poor immune response resulting primarily in low-affinity IgM antibodies. In a previous publication we introduced the lysibody approach to address this shortcoming. Lysibodies are engineered molecules that combine a high-affinity carbohydrate-binding domain from bacterial or bacteriophage origin and an Fc effector portion of a human IgG antibody, thus directing effective immunity to conserved bacterial surface carbohydrates. Here, we describe the first example of a lysibody containing the binding domain from a bacteriocin - lysostaphin. We also describe the creation of five lysibodies with binding domains derived from phage lysins, directed against Staphylococcus aureus The lysostaphin and LysK lysibodies showed the most promise and were further characterized. Both lysibodies bound a range of clinically important staphylococcal strains, fixed complement on the staphylococcal surface, and induced phagocytosis of S. aureus by macrophages and human neutrophils. The lysosta...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research