Rapid and Reliable Detection of Antimicrobial Peptide Penetration into Gram-Negative Bacteria Based on Fluorescence Quenching

In this paper, we describe a rapid flow cytometry method to identify antimicrobial peptides that are internalized into bacterial cells and differentiate them from those that are membrane active. The method was applied to fluorescently labeled Bac7(1-35) and polymyxin B, whose mechanisms of action are, respectively, based on cell penetration and on membrane binding and permeabilization. Identification of peptides with the former mechanism is of considerable interest for the intracellular delivery of membrane-impermeant drugs.