20.500.12556/RUL-107889 Strukturna raznolikost in aktivnost aminoglikozidnih antibiotikov Structural diversity and activity of aminoglycoside antibiotics Aminoglikozidni (AG) antibiotiki so antibiotiki širokega spektra, zgrajeni iz derivatov ciklitola ter modificiranih sladkorjev. Uporabni so za zdravljenje okužb s po Gramu negativnimi bakterijami. Prav tako AG antibiotiki predstavljajo potencial za zdravljenje genskih bolezni. Problemi njihove uporabe pa so nefrotoksičnost, ototoksičnost ter bakterijska odpornost. Zaradi tega se jih redko uporablja v klinični praksi. AG antibiotiki se vežejo na 16S rRNA in povzročijo napačno branje mRNA in inhibicijo translokacije. Izjema glede na mehanizem delovanja ter zgradbo je apramicin. Zadnje raziskave so pokazale, da je apramicin manj ototoksičen v primerjavi z ostalimi AG antibiotiki. Zaradi pojava odpornosti na AG antibiotike ter nižje učinkovitosti proti mikrobom iz skupine ESKAPE ponovno raste interes za razvoj AG antibiotikov nove generacije. V tem diplomskem delu smo naredili pregled razvoja AG antibiotikov, njihove biosinteze, s poudarkom na streptomicinu, gentamicinu ter apramicinu, mehanizma delovanja ter bakterijske odpornosti na AG antibiotike. Prav tako smo predstavili novosti v razvoju klinično uporabnih AG antibiotikov. Aminoglycoside (AG) antibiotics are potent broad-spectrum antibiotics, made up of cyclitol derivatives and modified sugars. They are used to treat infections with Gram-negative bacteria. AG antibiotics also have potential to be used for the treatment of genetic diseases. However, the problems with their usage are nephrotoxicity, ototoxicity and bacterial resistance. For that reason, they are rarely used in clinic. AG antibiotics bind to 16S rRNA and cause mRNA misreading and inhibition of translocation. When considering mode of action and structure, apramycin differs when compared to other AG antibiotics. Recent studies also revealed that apramycin has lower ototoxic activity compared to other AG antibiotics. Due to the increasing occurrence of resistance to AGs and thus reduced effectiveness against pathogens from the ESKAPE panel there is rising interest in the development of novel AG antibiotics. In this diploma work, we have reviwed development of AG antibiotics, their biosynthesis, with particular emphasis on streptomycin, gentamycin and apramycin. We have also presented mechanism of action and resistance to AG antibiotics and recent advancement in the development of clinically useful aminoglycoside antibiotics. aminoglikozidni antibiotiki ototoksičnost nefrotoksičnost biosinteza mehanizem delovanja bakterijska odpornost aminoglycoside antibiotics ototoxicity nephrotoxicity mechanism of action bacterial resistance biosynthesis true false false [J. Kralj] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2019-06-02 07:45:36 2019-06-02 07:45:39 2022-08-19 03:51:27 0000-00-00 00:00:00 2019 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 604.4:615.332(043.2) 163791 9233785 7052.pdf 7052.pdf 1 E1CBD4FCFC7AC202A2D02C97EB36AE7E 7957159eb374cf5ef8e6c826f1d688d913a7bf8e32721695248f8731c50f9c49 874412d3-a1b6-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=118777 Biotehniška fakulteta 0 0 0