Investigation of anti-quorum sensing and anti-biofilm activities on pseudomonas aeruginosa of peltigera species by lichen and endolichenic fungus specimens in vitro and in silico methods

Pseudomonas aeruginosa is an opportunistic pathogen bacteria that can be resistant to multiple antibiotics due to its biofilm forms responsible for acute and chronic infections. The Quorum Sensing (QS) mechanisms is associated with antibiotic resistance, biofilm formation, and the release of virulence factors. Therefore, there is a need for new QS inhibitors (QSI) that can inhibit intracellular and intercellular communication and the QS-related biofilm form without suppressing the growth of bacteria and causing death stress. In this study, the QSI potentials of n-Hexane extracts of lichens and ethyl acetate extracts of endolichenic fungus (ELF), which produce secondary metabolites with unique medicinal drug properties, were investigated. By creating a lichen secondary metabolite library, therapeutic and toxicity tests were performed, and then molecular docking simulations of 179 metabolites that do not show any toxicity were performed with the LasI/LasR, RhlR and PqsR receptor proteins involved in the P. aeruginosa QS system. Ten lichen metabolites belonging to the genus of Peltigera were determined to have the most successful binding energy. As a result of in silico findings, the species belonging to Peltigera genus, which are thought to have high in vitro activities, were collected from Artvin and Bursa regions, and morphological identifications were performed, and then ELF isolation and molecular identifications of ELF's were made from the thalli of these lichen species The extracts of lichens and ELFs, obtained from Peltigera species, were examined against P. aeruginosa PAO1 CECT4122 for anti-bacterial, anti-biofilm effects and lasB-gfp, rhlA-gfp and pqsA-gfp biomonitor strains for anti-QS effects. In particular, high QSI and anti-biofilm potentials against P. aeruginosa were detected for the extracts of P. horizontalis and ELF28 isolated from P. horizontalis and identified as Penicillium sp. When the results were evaluated, the consistency in in silico and in vitro studies was observed. It is thought that the extracts of Peltigera and its ELFs may alternatively have the potential to contain new QSI molecules against antibiotic resistance problem and thus, in aid for future studies, this thesis is expected to contribute to academic literatüre.