Določanje protibakterijskega delovanja knjižnice spojin na različne seve Enterococcus faecalis

Medved, Mia (avtor), Hrast Rambaher, Martina (mentor), Golob, Majda (komentor)

Bakterije predstavljajo ene izmed najpomembnejših povzročiteljev nalezljivih bolezni pri ljudeh in živalih, njihovo obvladovanje pa otežuje naraščajoča odpornost proti antibiotikom. Med klinično najpomembnejšimi povzročitelji okužb, povezanih z zdravstvom, je tudi bakterija vrste Enterococcus faecalis, oportunistična grampozitivna bakterija, povzročiteljica okužb sečil, ran, septikemije in endokarditisa. Njena sposobnost tvorbe obstojnih biofilmov, preživetja v zahtevnih okoljih ter razvoja večkratne odpornosti proti protibakterijskim učinkovinam predstavlja pomemben terapevtski izziv in poudarja potrebo po iskanju novih protimikrobnih pristopov. Cilj magistrskega dela je bil oceniti protibakterijsko delovanje izbranih spojin iz knjižnice spojin Fakultete za farmacijo Univerze v Ljubljani na tri različne seve bakterije E. faecalis (EFS). Pri kliničnih izolatih EFS 35-1469 in EFS 25-529 ter referečnemu sevu EFS RDK 057 smo določili njihovo občutljivost za antibiotike, preučili sposobnost tvorbe biofilmov v različnih pogojih ter ocenili protibakterijsko učinkovitost izbranih spojin za posamezne seve. V eksperimentalnem delu smo najprej ovrednotili delovanje 30 GDL-spojin, pri čemer jih je 19 izkazalo aktivnost proti vsaj enem izmed testiranih sevov E. faecalis. Protibakterijsko delovanje GDL-spojin smo opredelili z določanjem njihove minimalne inhibitorne koncentracije (MIK). Med spojinami z močnim zaviralnim učinkom so bile spojine GDL-50, GDL-59, GDL-66, GDL-88, GDL-89, GDL-90, GDL-95, GDL-101 ter GDL-102, ki jih uvrščamo v razred N-tiosubstituirani β-laktamov. V nadaljevanju smo izvedli obsežen presejalni test 840 spojin iz knjižnice spojin Fakultete za farmacijo in njihovo delovanje preverili na vseh treh izbranih sevih. Skupno je 50 spojin pokazalo protibakterijsko aktivnost proti vsaj enemu izmed testiranih sevov, kar predstavlja 5,95 % celotne knjižnice. Rezultati primerjave treh različnih sevov E. faecalis so pokazali tudi izrazite razlike v sposobnosti tvorbe biofilma, pri čemer je bila le-ta močno odvisna od uporabljenega gojišča. Iz tega je razvidno, da je sposobnost tvorbe biofilma različnih sevov iste vrste bakterije heterogena in izrazito pogojena z okoljskimi dejavniki.

• Jezik: Slovenski jezik
• Ključne besede: Enterococcus faecalis, protibakterijsko delovanje, biofilm, knjižnica spojin, minimalna inhibitorna koncentracija
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2026
• PID: 20.500.12556/RUL-181705
• Datum objave v RUL: 14.04.2026

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Antibacterial activity determination of compounds library against different strains of Enterococcus faecalis

Izvleček

Bacteria represent the most important causative agents of infectious diseases in humans, and their control is increasingly hindered by rising antibiotic resistance. Among the clinically most relevant hospital-associated pathogens is Enterococcus faecalis, an opportunistic Gram‑positive bacterium responsible for urinary tract infections, wound infections, bloodstream infections, and endocarditis. Its ability to form persistent biofilms, survive in harsh environmental conditions, and develop multidrug resistance poses a significant therapeutic challenge and highlights the need for novel antimicrobial strategies. The aim of this master’s thesis was to evaluate the antibacterial activity of selected compounds from the Faculty of Pharmacy University of Ljubljana compound library against three different E. faecalis strains. For the clinical isolates EFS 35‑1469 and EFS 25‑529, as well as the reference strain EFS RDK 057, we determined antibiotic susceptibility, examined their biofilm‑forming capacity under various conditions, and assessed the antibacterial effectiveness of the selected compounds on each strain. In the experimental part, we first evaluated the activity of 30 GDL compounds, of which 19 showed antibacterial effects against at least one of the tested E. faecalis strains. The antibacterial effect of the GDL compounds was defined by determining their minimum inhibitory concentration. Compounds with the strongest inhibitory activity included GDL‑50, GDL‑59, GDL‑66, GDL‑88, GDL‑89, GDL‑90, GDL‑95, GDL‑101, and GDL‑102, all belonging to the class of N‑thiosubstituted β‑lactams. Subsequently, we performed an extensive screening of 840 compounds from the Faculty of Pharmacy compound library and tested their activity against all three selected strains. In total, 50 compounds exhibited antibacterial activity against at least one strain, representing 5.95% of the entire library. Comparison of the three E. faecalis strains also revealed pronounced differences in their ability to form biofilms, which were strongly dependent on the growth medium used. These findings demonstrate that biofilm formation among strains of the same species is heterogeneous and highly influenced by environmental factors.

• Ključne besede: Enterococcus faecalis, antibacterial activity, biofilm, compound library, minimum inhibitory concentration