D-amino acid mediated recruitment of endogenous antibodies to bacterial surfaces.

Abstract

The number of antibiotic resistant bacterial strains has been continuously increasing over the last few decades. Nontraditional routes to combat bacteria may offer an attractive alternative to the ongoing problem of drug discovery in this field. Herein, we describe the initial framework toward the development of bacterial d-amino acid antibody recruitment therapy (DART). DART represents a promising antibiotic strategy by exploiting the promiscuity of bacteria to incorporate unnatural d-amino acids and subsequently recruit antibodies to the bacterial surface. The conjugation of 2,4-dinitrophenyl (DNP) to various d-amino acids led to the discovery of a d-amino acid that specifically tags the surface of Bacillus subtilis and Staphylococcus aureus for the recruitment of anti-DNP antibodies (a highly abundant antibody in human serum). This system represents a novel strategy as an antibacterial therapy that targets planktonic Gram-positive bacteria.