Esculentin-1a(1-21)NH2 and its diastereomer: antibacterial and immunomodulating activities

Microbial resistance to conventional antibiotics has become a major challenge. In this context, naturally-occurring antimicrobial peptides (AMPs) hold promise for the development of new drugsagainst microbial infections, including those caused by the bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) sufferers. Here we report on the in vitro activities of the frog-skin derived AMP Esculentin-1a(1-21)NH2 [Esc(1-21)], and its diastereomer Esc(1-21)-1c, containing two D-amino acids, on both macrophages and bronchial cells, which express either the functional or the ΔF508 mutant of the CF transmembrane conductance regulator (1). We found that the diastereomer is significantly less toxic; has significantly higher efficacy in killing intracellular Pseudomonas; has a higher activity in promoting migration of bronchial cells; disaggregates and detoxifies the bacterial lipopolysaccharide. These results support further studies towards the development of the Esc(1-21)-1c for local treatment of P. aeruginosainduced lung infections. This work was funded by Italian Cystic Fibrosis Research Foundation (FFC #11/2014).