Targeting bacterial cell wall carbohydrates

Targeting bacterial cell wall carbohydrates
 

The cell walls of Gram-positive bacteria contain numerous surface carbohydrates that are often highly conserved across species, providing a potential therapeutic target for the attachment of high-affinity antibodies. However, the poor immune response provoked by these bacterial targets has made obtaining such antibodies a challenge.

Researchers demonstrate the ability of binding domains from autolysins and lysins—enzymes that break down bacterial cell walls—to bind with the human antibody IgG fragment crystallizable region. The resulting molecule, termed a lysibody, is a functional homodimer that binds with high-affinity and specificity to carbohydrate determinants on the bacterial surface.

Furthermore, the authors demonstrate the reproducibility of the approach with three separate binding domains for methicillin-resistant Staphylococcus aureus (MRSA). The lysibodies induced complement fixation on the surface of MRSA cells, and promoted phagocytosis and killing of MRSA by macrophages and human polymorphonuclear neutrophils.

Lysibodies also protected mice from infection with MRSA in two models. According to the authors, lysibodies might aid the treatment of a range of bacterial infections.

http://www.pnas.org/content/early/2017/04/19/1619249114

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