Novel analogs of human beta defensins 1 and 3 showed enhanced antimicrobial activity

Defensins, antimicrobial peptides, form part of our innate immune system; two classes are found in humans, alpha- and beta-defensins. Epithelial cells secrete human beta defensins (hBDs). They kill bacteria and fungi in a quite aspecific way and/or by pore formation in the target membrane; they also exert chemotactic properties towards immature dendritic cells and T-cells, coupling the human innate immune response to the cellular response. A properly operating immune system is necessary in the prevention and elimination of infections, like lung infections, or viral infections. Since defensins are expressed in the airways and since they have chemotactic and antimicrobial properties, they are good candidate modifier genes for lung diseases. It is well known that, the antibacterial activity of beta-defensin 1, 2 and 4 is modulated by the salt concentrations; the high levels of NaCl observed, for example in the respiratory layer of cystic fibrosis patients, can inhibit the activity of beta-defensins, contributing to chronic infections and bacterial colonisation. On the other hand, the antibacterial activity of human beta defensin 3 is not modulated by the salt concentration of the medium. To increase our insight into the pathophysiology of beta defensins and to clarify the potential role of these peptides as therapeutic targets, we performed in vitro tests to evaluate the antimicrobial (against Pseudomonas aeruginosa), pro-chemotactic (toward neutrophils) and the antiviral activity (against herpes simplex virus) of beta-defensin variants obtained by chemical synthesis.