Antimicrobial peptide-metal ion interactions - a potential way of activity enhancement

Increasing bacterial and fungal drug resistance requires novel, effective antimicrobial treatments to be actively sought. Because of a general lack of resistance towards antimicrobial peptides (AMPs), they are being relied on as a novel class of therapeutics aiming to conquer drug-resistant bacteria and fungi. There are numerous ways in which AMPs might interact with pathogens, such as membrane disruption, production of ROS, inhibition of cell wall, nucleic acid and protein synthesis or by the withdrawal of essential metal ions. Biologically indispensable metal ions have a dual effect on the activity of antimicrobial peptides: (i) AMPs bind them, so that microbes cannot get enough metals essential for their life and virulence (withdrawal of metal ions, nutritional immunity) or (ii) AMPs need the given metal ion as a booster of their antimicrobial activity (metal ions affect the AMP charge and/or structure). We discuss both strategies, focusing on AMP metal binding mode, structure, thermodynamics and mode of action.