Live-Cell Imaging and Analysis Shed Light on the Complexity and Dynamics of Antimicrobial Peptide Action

sometimes devastating diseases in humans, animals, and crops. Furthermore, resistance against antimicrobial drugs is steadily increasing. There is thus an urgent need to discover new antimicrobial drugs and drug targets. Antimicrobial peptides (AMPs) are widespread in nature and produced naturally by animals, plants, fungi, and bacteria (Zasloff, 2002). These secreted peptides typically act as broad spectrum antibiotics as part of the innate immune systems of these organisms. AMPs that possess high activity against microbial pathogens are attracting great interest for use as novel therapeutic agents to prevent and treat microbial diseases (Brogden, 2005; Hancock and Sahl, 2006). The cell-penetrating properties of many AMPs facilitate them reaching intracellular targets which, in most cases, are unknown and may be novel (Marcos and Gandía, 2009; Nicolas, 2009). Numerous candidate AMP-based drugs for use in humans, animals, and crops will undoubtedly appear over the next decade. A mechanistic understanding of their mode-of-action will be essential to underpin their use as new antimicrobial drugs, to identify novel drug microbial targets, and assist the rational design of more powerful and specific AMPs and peptidomimetics.