The recently demonstrated mechanisms show promise for a new therapeutic approach for the treatment of acute and chronic infections of skin and soft tissue infections. "In particular, chronic skin infections are a major challenge for treatment, as a cure is often impossible or very lengthy," explains Günther Weindl. In addition, increasing antibiotic resistance is, as recently confirmed by the World Health Organization, "one of the greatest threats to global health." Weindl stressed that in this regard, and given the increasing global spread of multi-resistant pathogens, the synthetic peptides could possibly offer a new treatment option for these diseases because resistance mechanisms against the peptides are not expected.
In their study, the researchers investigated two peptide drugs, Pep19-2.5 and Pep19-4LF, which are characterized by efficient neutralization of highly conserved pathogenic structures of the bacterial cell wall, particularly of lipopolysaccharides and lipoproteins and -peptides, as well as by anti-microbial and anti-inflammatory activity. Previous studies done at the Research Center Borstel have shown, among other things, that Pep19-2.5 has a very good effect against blood poisoning (sepsis) in animal models. The current study addressed the potential application in skin infections. The in vitro studies done in collaboration with biophysicists from Borstel demonstrate strong inhibition of inflammatory processes for both peptides in skin and immune cells. These processes were triggered by bacterial cell wall components. At the same time the peptides suppress the activation of immune cells that play an essential role in chronic inflammation and have a very low toxicity to human cells. In addition to the anti-inflammatory effect, the scientists identified an additional mechanism of action. The peptides promote cell migration of keratinocytes, an important process during wound healing. An artificially produced "wound" in cell cultures is closed significantly faster with very low concentrations of peptide compared with the untreated control sample. It appears that certain endogenous receptors in keratinocytes, so-called purine receptors, are significantly involved in this additional mechanism. As the next step, Weindl and his colleagues plan to test the peptides in three-dimensional infection and wound healing models of the skin and to elucidate the molecular mechanism of the migration-promoting effect.
Anja Pfalzgraff, Lena Heinbockel, Qi Su, Thomas Gutsmann, Klaus Brandenburg & Günther Weindl: Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration, in: Scientific Reports. URL: www.nature.com/articles/srep31577, DOI: 10.1038/srep31577.
Prof. Dr. Günther Weindl, Institute of Pharmacy, Pharmacology, and Toxicology, Freie Universität Berlin, Tel.: +49 30 838-54372, Email: Guenther.Weindl@fu-berlin.de