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Treatment options for untreatable amoeba Naegleria fowleri
Veselý, Martin ; Mach, Jan (advisor) ; Arbon, Dominik (referee)
Naegleria fowleri is a free-living protist which can penetrate the body of a previously healthy person and cause meningoencephalitis. The rapid course, disproportionately strong immune response and the lack of effective drugs are the reasons why this disease almost always ends fatally. Due to the relative rarity of this disease, it is not lucrative for pharmaceutical companies to develop a completely new drug. The only way to search for effective drugs is to test those that have already been approved for another purpose. However, clinical tests are not possible due to the low morbidity and rapid course of the disease, and research in this area is thus limited to animal models of the disease and evaluation of the effect of drugs against the pathogen in vitro. Currently used medication includes drugs that are highly toxic or poorly penetrate the site of inflammation. In the future, more effective chemotherapy against N. fowleri and more gentle towards patient could be used. This work summarizes knowledge about pathogenic amoeba, currently used drugs and presents new experimentally tested therapeutics.
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The effect of amoeba predation on the evolution of virulence in human pathogenic microorganisms
Drncová, Eliška ; Šuťák, Róbert (advisor) ; Konupková, Anežka (referee)
Amoebae act as one of the main regulators of microbial communities, where, as a result of their predation, selection pressure is exerted for the emergence of defence mechanisms to achieve resistance. This adaptation allows microorganisms to randomly infect the human body and successfully defend against components of innate immunity, especially macrophages, which, like amoebae, are phagocytic cells. The manifestation of virulence in opportunistic pathogens is due to conserved macrophage pathways used for degradation of ingested material, which the microorganism has already encountered in amoebae. Because of this similarity, amoebae can be used to investigate the interaction between a pathogen and its host, which includes research on the virulence mechanisms of many human microbial infections. Among the most extensively studied organisms whose pathogenicity results from long-term interaction with amoebae are the bacterium Legionella pneumophila and the microscopic fungus Cryptococcus neoformans, with very different virulence strategies and manifestations. Understanding the evolutionary context and the advantages that microorganisms gain during interaction with amoebae informs us about the origins of virulence of opportunistic human pathogens.
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Naegleria: from free-living protist to brain eating deadly pathogen
Matějková, Magdalena ; Mach, Jan (advisor) ; Marková, Lenka (referee)
N. fowleri is mostly a free-living amoeboflagellate which, in favorable conditions, can occasionally adopt a parasitic lifestyle. In such cases, the amoeba becomes causative agent of primary amoebic meningoencephalitis, a severe and largely fatal disease occurring in several mammals including humans. The treatment of this disease is complicated by many unwanted side-effects of available drugs and a lack of prompt diagnostic methods. Within the Naegleria genus, N. fowleri is the only human pathogen. According to up-to-date knowledge, the pathogenicity of this species is due to its metabolic properties as well as to a particular set of proteins expressed by this protist. Besides a wide scale of enzymes, some of these proteins participate in the formation of cellular structures which are crucial for the pathogenesis. All these particularities should be targeted in a search for a better treatment. The thesis is focusing on a comparison of N. fowleri with related species N. gruberi and N. lovaniensis, stressing out the differences of N. fowleri from these non-pathogenic species. Key words: Naegleria fowleri, primary amoebic meningoencephalitis, immune response, pathogenesis, facultative parasitism
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Replication strategies of newly discovered giant viruses of amoebas
Blaško, Michal ; Forstová, Jitka (advisor) ; Sýkora, Michal (referee)
Giant viruses are a group of viruses with genome composed of double-stranded DNA molecule. They are characterized by the creation of giant viral particles, the size of which varies between 150-1500 nm. Also, their genomes are huge reaching sizes of up to 2,5 Mbp. The viruses replicate either in the cytoplasm or they exploit for their replication both nucleus and cytoplasm. Therefore, they are called, nucleocytoplasmic large DNA viruses (NCLDVs). During their replication cycle, the giant viruses induce the creation of viral factories, which provide morphogenesis of new virions. The aim of this thesis is to summarise current knowledge of selected representatives of the giant viruses, and to describe their replication strategies. Furthemore, this work aims to discuss discoveries made in relation to this particular group if viruses. Thanks to the discovery of giant viruses, another group of small viruses was identified - the so-called virophages (viruses of viruses). Virophages have the ability to take advantage of the giant virus infecting an amoeba to realize their own replication strategy. In some members of the Mimiviridae family there was described a presence of an genome element providing a unique way of immunoprotection of giant viruses from being infected by the Zamilon virophage. Key words:...
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