Antimicrobial Peptides

Amanda Rice
New York University

As multidrug resistant bacterial strains emerge in increasing numbers, the need for new kinds of antibiotics is as pressing as ever. For the last few decades it has been known that all manner of multicellular organisms defend themselves from infection by synthesizing molecules known as antimicrobial peptides, molecules that kill bacteria and some fungi by interacting with and disrupting the membrane at the cell surface of invading microorganisms. It is thought that membrane disintegration, which kills the target cell, can only be achieved after the peptides coat the cell surface fairly evenly, a phenomenon that necessitates a relatively high concentration of peptide. While this is a viable solution to infection in the body, because peptides can be released in close vicinity to infectious cells, it makes them impractical for use as drugs against systemic infection, because at high enough concentrations they can become toxic to cells of the host as well. Therefore, we have devised a strategy involving the use of chemical means to tie together a number of the peptides to form a complex, in hopes that when such a complex lands on the bacterial membrane, it will create the effect of an already high local concentration, decreasing the effective killing concentration. Thus far we have achieved some success in increasing the effectiveness of several peptides, both naturally occurring and of our own design, by tethering them together to form complexes of two or more single peptides, and we hope to improve upon these results in the future.