Immune System Enlisted For Antibacterial Therapy

When scientists feed bacteria antigen-containing d-amino acids, the microbes incorporate the molecules into their cell walls, making them targets for immune cells. Marcos M. Pires and his colleagues of Lehigh University report that this development is a first step toward a new antibacterial strategy that doesn’t kill pathogenic bacteria directly but recruits the immune system to do the dirty work (ACS Chem. Biol. 2014, DOI: 10.1021/cb5002685). The strategy takes advantage of the ability of some microbial enzymes to grab d-amino acids from the environment and incorporate them into the peptidoglycans of the bacterial cell wall. The researchers synthesized d-lysine attached to the antigen 2,4-dinitrophenyl (DNP), which is recognized by antibodies that occur naturally in most people. To test the approach, the researchers added macrophages to a culture containing the lysine-DNP conjugate, a DNP antibody, and fluorescently labeled Bacillus subtilis. The macrophages glowed twice as bright as those in cultures without the d-amino acid, indicating that the macrophages were more likely to engulf bacteria that incorporated the conjugate into their peptidoglycans. Daniel B. Kearns of Indiana University, Bloomington, thinks the idea is clever but says a drawback is that it might also target friendly bacteria in the body. He also wonders whether the effect would be potent enough to conquer a bacterial infection.