DCAP Antibiotic Takes Aim At Membrane Targets

Standard antibiotics are usually fine for fighting most fast-growing bacteria, but they typically have trouble treating persistent infections caused by slow-growing dormant and biofilm-associated bacteria. Now, researchers led by Douglas B. Weibel of the University of Wisconsin, Madison, have discovered a broad-spectrum antibiotic capable of killing these types of bacteria (J. Am. Chem. Soc., DOI: 10.1021/ja302542j). The compound, known as DCAP, battles the slow growers by reducing their transmembrane potential and increasing their membrane permeability. These processes disrupt the organization and integrity of the bacterial membrane and put essential membrane-associated proteins out of whack. Weibel and coworkers identified DCAP by high-throughput screening. The compound has no toxic effect on red blood cell membranes at concentrations at which it’s effective against bacteria, the researchers note, but they did observe some toxicity in studies with other types of human cells. They plan to address this problem by making DCAP analogs. The researchers also hope that, by studying DCAP’s structure-function relationship, they can develop design rules for potent membrane-targeting drugs that specifically attack bacterial cells.