Human and plant proteins as reservoirs of host defence peptides

Antimicrobial peptides (AMPs), known also as host defense peptides, are fundamental evolutionarily conserved components of innate immunity. Constitutively or inducibly expressed in response to invasion by pathogens, they operate synergistically with other defence molecules to combat infections. Despite differences in their size and sequence, many of them share a net positive charge at neutral pH, and fold into amphipathic structures, often after contact with bacterial surfaces. HDPs are attractive alternative candidates for antibiotic treatment, because they offer several advantages over the currently used drugs. They combat pathogens by targeting bacterial membranes, thus impairing essential membrane-related functions, and, in some cases, also target intracellular components. Due to their peculiar mechanism, the resistance towards these peptides would be difficult for the bacteria to develop. Several proteins, including proteins apparently not involved in immunity, can behave as sources of HDPs hidden in their primary structures and released by the action of host and/or bacterial proteases. Recently it has been developed a bioinformatic tool allowing to identify such “cryptic HDPs”. Analyzing a library of 4000 proteins, we have identified and studied several novel cryptic HDPs from human and plant. Among these, three human peptides (GVF27, ApoBS and ApoBL) show pharmacologically relevant properties like significant antimicrobial activity on a broad spectrum of bacteria (including some clinical isolates), very promising antibiofilm properties (both on pre-formed and attached biofilm), strong affinity for endotoxins as LPS and LTA and immunomodulatory properties on LPS induced murine macrophages, while two peptides from plant (IKY31 and IKY23) are strong anti-biofilm agents and not toxic against eukaryotic cells. Overall our data suggest that these new cryptic HDPs, could serve as leads for the design of innovative antimicrobials with immunostimulating and immunomodulatory properties.