Temporins and their synergism against Gram-negative bacteria and in lipopolysaccharide detoxification

AbstractRibosomally synthesized antimicrobial peptides (AMPs) represent an essential component of the ancient and non-specific innate immune system in all forms of life, with the primary role of killing infectious microorganisms. Amphibian skin is one of the richest storehouses for them. Each frog species produces its own set of peptides with up to 10 isoforms, as in the case of the species Rana temporaria. Nowadays, human health is facing two major threats: (i) the increasing emergence of resistant pathogens to one or more available drugs, and (ii) the onset of septic shock, which is associated with the release of lipopolysaccharide (LPS) from the cell walls of Gram-negative bacteria, particularly upon antibiotic treatment. AMPs are considered as potential new anti-infective compounds with a novel mode of action, because many of them can kill bacteria and, at the same time, neutralize the toxic effects of LPS. Recent studies have suggested that the production of large number of structurally similar AMPs within the same animal is a strategy used by nature to increase the spectrum of antimicrobial activities, by using combinations of the peptide's isoforms. The biological rationale for their coexistence within the same organism is discussed. In addition, the distinctive and attractive synergistic effects of temporins in both antimicrobial and anti-endotoxin activities are reviewed, along with their plausible underlying molecular mechanism