Characterization of new pleurocidin derivatives and determination of their antimicrobial, antibiotic and immunomodulatory effects in vitro and in vivo conditions

Antimicrobial resistance poses a serious threat to global public health by making it difficult or impossible to treat infections. One of the most important causes of antimicrobial resistance is biofilms. Therefore, it is of great importance to combat biofilms and discover new antibiofilm agents. In this thesis, the characterization, antimicrobial and antibiofilm properties of GK-11 and LF-12 peptides derived from pleurocidin peptide and their immunomodulatory effect in Caenorhabditis elegans model organism were evaluated. In our results, GK-11 inhibited the growth of Staphylococcus aureus (ATCC 43300) at 64 µg/mL and Pseudomonas aeruginosa (PAO1) at 256 µg/mL. Biofilm formation was inhibited at 32 µg/mL and 16 µg/mL, respectively. LF-12 inhibited the growth of S. aureus and P. aeruginosa at 256 µg/mL and biofilm formation in S. aureus at 8 µg/mL. The hemolytic and cytotoxic effects of GK-11 peptide, which has antibiofilm activity against both pathogens, were found to be low. It was determined that it had no toxic effect against C. elegans and increased survival in the presence of infection. In addition, GK-11 peptide showed immunomodulatory effect by decreasing the expression level of akt-1 gene in C. elegans. In conclusion, new antibiofilm peptide candidates were identified and their potential for use in biofilminduced infections was demonstrated. Keywords: Antibiofilm peptide, C. elegans, Immunomodulatory effect, Pleurocidin