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Metronidazole resistence in clinical cases of giardiasis.
Perglerová, Aneta ; Tůmová, Pavla (advisor) ; Uzlíková, Magdalena (referee)
Metronidazole (MTZ) targets a spectrum of anaerobic pathogens ranging from bacteria to eukaryotic parasites, including the protist Giardia intestinalis (Metamonada). Despite the long time and widespread use of MTZ, understanding giardiasis treatment failure (G-TF) is incomplete. Most of the knowledge was gained on laboratory-generated resistant lines or on clinical lines without data on the treatment outcome. In cooperation with Bulovka University Hospital in Prague, 70 giardiasis cases were followed between 2020-2023, of which 25.7% exhibited the G-TF. Giardia genotyping revealed that G-TF cases belonged to the same genetic group (assemblage B, mainly BIII); and G-TF cases were all imported, out of which 60% were from returning travellers from India. To test the hypothesis that resistance is genetically determined/associated with a transmissible genotype, genetic polymorphisms shared in Giardia G-TF samples in a set of genes involved in MTZ metabolism and detoxifications (NR1, NR2, prx1, hmp) were examined. The analysis revealed amino acid substitutions (K42E, K139R) in NR2 isolates of G-TF patients, which might affect protein structure. Also, a gene dosage effect as drug resistance co-variant/cause due to gene duplications or deletions of the hmp gene was tested. Results from dPCR revealed that...
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Cellular Protein Transport and Its Role in Patogenesis
Najdrová, Vladimíra ; Doležal, Pavel (advisor) ; Uzlíková, Magdalena (referee)
The main topic of this thesis are the protein secretion processes in several important human parasites - Toxoplasma gondii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp. and Giardia intestinalis. Described here are the parasite's and the host proteins which participate in the pathogenic processes involving the protein secretion. As shown here, the protein secretion into the host environment is one of key tools serving the parasite to survive within and manipulate the host organism. Interestingly, different parasitic organisms use functionally and evolutionary distinct strategies to fulfill this aim. Key words secretory pathway, translocon, signal sequence, Toxoplasma gongii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp., Giardia intestinalis
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Maintenance of chromosomes integrity in Giardia intestinails as a model organism.
Uzlíková, Magdalena ; Nohýnková, Eva (advisor) ; Lalle, Marco (referee) ; Stejskal, František (referee)
Giardia intestinalis is a protozoan causing diarrhea worldwide. Beside its medical importance, it is evolutionary distant protist with two nuclei within a cell adapted for parasitic life in the environment poor of oxygen. Its genome is small and compact in term of gene content and size. It is therefore an attractive model organism for studies of minimal requirements for cellular processes. Present work brings new partial information on different levels of chromosome integrity maintenance of this parasite. Our study presents characteristics of chromosome termini and their protection. We localized telomeres during all stages of the trophozoite cell cycle and determined the length of Giardia telomeres ranging from 0.5 to 2.5 kb, we proved an existence of an active telomerase enzyme synthesizing telomeric repeats in in this parasite, despite the fact that giardial telomerase is structurally divergent. Present data support the view that the chromosomal termini in Giardia are maintained in a conservative manner that is common to other eukaryotes. We described effects of commonly used drug for treatment of anaerobic infections, metronidazole, on DNA and cell cycle progression in susceptible and resistant cell lines. Incubation of cells with this drug causes phosphorylation of histone H2A in cell nuclei...
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Cellular Protein Transport and Its Role in Patogenesis
Najdrová, Vladimíra ; Doležal, Pavel (advisor) ; Uzlíková, Magdalena (referee)
The main topic of this thesis are the protein secretion processes in several important human parasites - Toxoplasma gondii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp. and Giardia intestinalis. Described here are the parasite's and the host proteins which participate in the pathogenic processes involving the protein secretion. As shown here, the protein secretion into the host environment is one of key tools serving the parasite to survive within and manipulate the host organism. Interestingly, different parasitic organisms use functionally and evolutionary distinct strategies to fulfill this aim. Key words secretory pathway, translocon, signal sequence, Toxoplasma gongii, Plasmodium falciparum, Trypanosoma cruzi, Leishmania spp., Giardia intestinalis
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