Virtually all AMPs are cationic and amphiphilic, which determines their mode of action. Although the modes of action of AMPs on their target bacteria are complex, they can be divided into membrane and non-membrane disruptive.
Membrane disruptive
Amphipathic and helical AMPs (like some of DermaGen’s pipeline AMPs) are able to interact with bacterial surface components, leading to conformational changes (such as helix formation), which in turn facilitates hydrophobic membrane interactions, membrane destabilization and finally, bacterial death. Peptide binding and membrane lysis may occur also with peptides not undergoing such conformational changes, including several of those developed by DermaGen.
Antimicrobial peptides bind to and permeabilize bacterial membranes.
Laboratory microscope photos and electron micrographs showing the effects of a DermaGen AMPs can be seen below.
DermaGen’s AMPs bind to bacteria and fungi.
Panel A: The common wound bacterium Enterococcus faecalis (upper left) and the fungal pathogen Candida albicans (upper right) were subjected to fluorescent AMPs and the binding is visualized as fluorescence from the microbial cells (bottom).
Panel B: Electron microscopy analysis of Pseudomonas aeruginosa bacteria subjected to one of DermaGen´s AMPs (left; control, right; treated bacteria). As can be seen, addition of the AMP (right) results in disruption of the bacterial membrane.
Non-membrane disruptive
There is increasing evidence to indicate that antimicrobial peptides also attack intracellular targets. Once in the cytoplasm, the translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. For example, AMPs pleurocidin and dermaseptin, inhibit nucleic acid and protein synthesis without damaging the E. coli cytoplasmic membrane