The antibacterial activity and therapeutic potential of theamphibian-derived peptide TB_KKG6K
Antimicrobial peptides (AMPs) have great potential to be developed as topical treatments for microbial infections of the skin, including those caused by the gram-positive human pathogen Staphylococcus aureus. Among the AMPs, temporin B (TB) is of particular interest. This 13-amino-acid-long cationic peptide is secreted by the granular glands of the European frog Rana temporaria and represents a primary line of defense against invading pathogens. The objective of this study was to investigate the antibacterial efficacy and the mode of action of the synthetic TB analog, TB_KKG6K, in a drug-resistant clinical isolate of S. aureus and assess the peptide’s tolerance and curative potential in an in vitro infection model using three-dimensional human epidermis equivalents (HEEs). The results revealed a high bactericidal efficacy of TB_KKG6K at low micromolar concentrations. The peptide perturbed the bacterial cell membrane integrity by permeabilization and depolarization. TB_KKG6K showed no toxicity in the inverte brate mini-host model Galleria mellonella and a high level of tolerance when topically applied in HEEs. Importantly, the therapeutic potential of TB_KKG6K was confirmed in HEEs infected with S. aureus. The topical application of TB_KKG6K significantly reduced the bacterial load and lowered the pro-inflammatory response in the infected HEEs.
These findings reinforce the antibacterial potential and therapeutic efficacy of TB_KKG6K
against S. aureus infection, particularly in the context of a cutaneous infection.
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