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Antiparasitic and antimycotic effect of different iron chelators
Šipková, Anna ; Šuťák, Róbert (advisor) ; Kuthan, Martin (referee)
Iron plays a key role in many metabolic pathways in the cell, but it may become toxic at higher concentrations. Therefore, the maintenance of iron homeostasis is crucial for cell viability and is strictly regulated. This element has also an important role in the host-parasite interaction. Parasites are fully dependent on iron uptake from the host environment. Iron uptake is a very difficult process thanks to effective sequestration of the host's iron supplies, which makes iron almost inaccessible to parasites. Imported iron is mostly transported to the mitochondria where it is necessary for its proper function. This work is focused on the effect of modified chelators on pathogenic fungi and the chosen kinetoplastid parasites, which cause serious human diseases. These diseases are becoming a great threat due to emerging drug resistances. Modified chelators are able to target mitochondrial functions and affect iron homeostasis, which can lead to a promising antiparasitic and antimycotic effect. Modified chelators in tested organisms can inhibit their gorwth even in nM concetrations, affect mitochondrial respiration, membrane potential and membrane permeability. Thanks to mitochondrial targeting the potency was much higher compared to the unmodified compounds. This work contains also research of new...
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Alcohol dehydrogenases in parasitic protists
Šipková, Anna ; Mach, Jan (advisor) ; Smutná, Tamara (referee)
Bachelor's thesis summarizes alcohol dehydrogenases mainly in parasitic protists. These widespread enzymes have been identified in several organisms ranging from bacteria to human. Thanks to the diversity of the enzyme's structure and substrate specificity is its function variable. Structure of the model zinc-containing Adh1 Saccharomyces cerevisiae is tetrameric. Enzymes are responsible for reversible oxidation of alcohols to aldehydes or ketones with concomitant reduction of NAD(P)+ as a cofactor. In most organisms, Adh appears in several types. Classification of Adhs is quite difficult and incomplete due to the investigation progress. The current classification includes three groups: MDR ("medium chain" Adh), SDR ("small chain" Adh) and iron-containing Adh. Adhs in parasitic protists have a specific role in the flexibility of metabolism and the adaptability to environmental changes in the host. This thesis deals especially with anaerobic parasites, where Adh is important in fermentation metabolism. Adh also figures in the resistance to drugs like in Trypanosoma cruzi or Tritrichomonas foetus. Recently, Adh has become a promising enzyme for a biotechnological application like in pharmaceutical or chemical industry. Keywords: Alcohol dehydrogenases, classification, parasitic protists, resistance
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