Till Örebro universitet

Modern medicine relies on the access to effective antibiotics. They are not only necessary to treat infections but enable the invasive therapies and surgeries to which we are accustomed today. Hence, the significant rise of bacterial resistance towards antibiotics threatens to topple a large part of global health care. This thesis investigates the potential of two antimicrobial peptides (AMPs), namely the bacteriocin Plantaricin NC8 ∝β (PLNC8 ∝β), and a novel synthetic lipopeptide derived from PLNC8 β termed 6-C5-N, for the topical treatment of infected wounds. Through a series of studies, the effectiveness and broad-spectrum activity of both these AMPs in vitro is demonstrated, and their influence on human cells in regard to toxicity, inflammation and survival is evaluated. Both AMPs exhibit low cytotoxicity in vitro and modulate important cytokines and growth factors in relation to infection and wound healing. Furthermore, utilizing ex vivo and in vivo models, it is demonstrated that 6-C5-N is an interesting candidate for the topical treatment of infected wounds. Additionally, a possible explanation of the complex problem with bacterial resistance to AMPs is presented, by demonstrating how extracellular divalent cations can be utilized by gram negative bacteria as protection against positively charged antibacterial peptides. In conclusion, PLNC8 ∝β and its derivative lipopeptide 6-C5-N are promising candidates for topical treatment of infected tissues and could play a role in the struggle against the development of antimicrobial resistance.