Immuno-targeting of Staphylococcus aureus via surface remodeling complexes

Agents with novel mechanisms of action are needed to complement traditional antibiotics. Towards these goals, we have exploited the surface-homing properties of vancomycin to tag the surface of Gram-positive pathogens with immune cell attractants in two unique modes. First, vancomycin was conjugated to the small molecule hapten 2,4-dinitrophenol (DNP) to promote bacterial opsonization. Second, we built on these results by improving the tagging specificity and mechanism of incorporation by coupling it to a sortase A substrate peptide. We demonstrated, for the first time, that the surface of Staphylococcus aureus (S. aureus) can be metabolically labeled in live Caenorhabditis elegans hosts. These constructs represent a class of promising narrow-spectrum agents that target S. aureus for opsonization and establish a new surface labeling modality in live host organisms, which should be a powerful tool in dissecting features of host-pathogen interactions.