A lesson from amphibian skin for the development of new anti-infective agents

Ribosomally-made antimicrobial peptides (AMPs) are key components of the innate immune response of all living organisms (1). Amphibian skin secretions represent one of the richest sources for such molecules, which are synthesized and stored within granules of holocrine-type glands and released upon stimulation (2). Recently, a particular attention has been devoted to the temporin family because of their unique properties: (i) they are among the smallest AMPs (10-16 residues) with the lowest number of cationic amino acids;; (ii) some isoforms display a fast membranolytic effect against bacteria, yeasts and protozoa of Leishmania genus (2); (iii) some others can neutralize the toxic effect of the lipopolysaccharide (LPS), by inhibiting TNF- release from LPS-activated macrophages; and (iv) they display among them a synergistic effect against Gram-negative bacteria to overcome microbial resistance imposed by the LPS-outer membrane (3,4); (v) the same temporin combinations can also synergi