Fluorescence and electron microscopy methods for exploring antimicrobial peptides mode(s) of action

Due to the increasing resistance of microbial pathogens to the available drugs, the identification of new antimicrobial agents with a new mechanism of action is urgently needed. In this context, cationic antimi- crobial peptides (AMPs) are considered promising candidates. Although there is evidence that, in contrast to conventional antibiotics, microbial membranes are the principal target of a large number of AMPs, thus making it difficult for the pathogen to acquire resistance, their mode(s) of action is not yet completely clear. Intense research is currently devoted to understand the effect(s) of AMPs on intact cells, either at sub-lethal or at lethal peptide concentrations, and fluorescence/electron microscopy techniques rep- resent a valid tool to get insight into the damage caused by these molecules on the morphology and membrane structure of the target cell. We here present an overview of some microscopic methodologies to address this issue.