Immuno-targeting of Gram-positive Pathogens via a Cell Wall Binding Tick Antifreeze Protein

Abstract

The human immune system employs several mechanisms to defend against pathogenic bacteria. However, pathogenic bacterial cells have evolved means to counter these responses, rendering our immune system less effective. Immunological agents that supplement or modulate the host immune response have proven to have powerful therapeutic potential, although this modality is less explored against bacterial pathogens. We describe the application of a bacterial binding protein to re-engage the immune system towards pathogenic bacteria. More specifically, a hapten was conjugated to a protein expressed by Ixodes scapularis ticks, called Ixodes scapularis antifreeze glycoprotein (IAFGP), that has high affinity for the D-alanine residue on the peptidoglycan of the bacterial cell wall. We showed that a fragment of this protein retained high surface binding affinity. Moreover, when conjugated to a hapten this conjugate led to the display of haptens on the cell surface of vancomycin-resistant Enterococcus faecalis. Hapten display then induced the recruitment of antibodies and promoted immune-cell mediated uptake of bacterial pathogens. These results demonstrate the feasibility in using cell wall binding agents as the basis of a class of bacterial immunotherapies against bacterial pathogens.