Tilte: Host Defense Mechanisms at Biological Membranes: Investigating the Triangle between Metallopeptides, Metal Ions, and Bioactive Lipids.
Abstract: Host-produced antimicrobial peptides are multifunctional molecules that exert crucial roles to prevent and fight infections. Not only can they directly eradicate pathogens by permeabilizing their membranes or targeting intracellular processes but they can also exhibit immunomodulatory activity, such as the chemotaxis of immune cells. The multiple functions of peptides in the piscidin family, the first host defense peptides to be discovered in mast cells, range from antibacterial, to antiviral, antifungal, anticancer, anti-inflammatory, and anesthetic activity. In our research, we perform biochemical and biophysical experiments to investigate piscidin’s molecular targets and mechanisms of antimicrobial action. Employing tools that include high-resolution solid-state NMR, neutron diffraction, oriented circular dichroism, permeabilization assays, biological-activity testing, and confocal microscopy, we map at the molecular and atomic levels the landscape of intrinsic structural features and environmental conditions such as metal ions and bioactive lipids that confer to a single peptide family a multiplicity of functions in support of host defense. These principles could be useful to design novel therapeutics that treat immune-related diseases and eradicate drug resistant bacteria.