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Current options of treatment for parasitic kinetoplastids
Čadková, Aneta ; Mach, Jan (advisor) ; Richterová, Lenka (referee)
Chagas disease, sleeping sickness and leishmaniasis are diseases occurring mainly in developing areas of Africa, America and Asia. They are caused by parasitic kinetoplastids from the genus Trypanosoma and Leishmania. These protozoans undergo morphologic transformations during their development leading to changes of their properties. They are characterized by complex mechanisms that allow them to evade the host's immunity. At the same time, because of these mechanisms and selection pressures, they are able to subsequently develop resistance to used drugs. The diseases caused by protozoa are classified as "neglected tropical diseases". The research and development of drugs against them is heavily underfunded. Currently used drugs are expensive, have a number of side effects, and due to lack of usage regulation develop resistance. The work first generally presents human parasites of the class Kinetoplastida. It further describes the treatment of diseases caused by the characterized species and focuses on a summary of currently used drugs, their mechanism, resistance and potential new drugs in clinical phases. Key words: kinetoplastids, Trypanosoma, Leishmania, treatment, disease, mechanism of action, resistance, nitroreductase
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Genotype influence on development of infections caused by Trypanosomatidae in mouse
Šíma, Matyáš
Parasitic protists of genera Trypanosoma and Leishmania are members of Trypanosomatidae family. In our studies, we investigated genetic influence on infections caused by these parasites in a mouse model. These diseases are on genetic level controlled by quantitative trait loci (QTLs), when the resulting phenotype is controlled by set of genes with small individual effect. As a mouse model for mapping of QTLs controlling these infections, we used recombinant congenic strains (RCS). Each RCS carry unique set of 12.5% of the genome from donor parental strain on genetic background of other parental strain. For mapping of QTLs controlling infections caused by Trypanosoma brucei brucei (T. b. brucei) and Leishmania tropica (L. tropica) and eosinophil infiltration into inguinal lymph nodes after Leishmania major (L. major) infection, we used RCS from CcS/Dem series, where STS is donor strain and BALB/cHeA is strain of genetic background. First, it was necessary to find suitable model strains for mapping. In all three studies, we selected RCS, which exceeded range of monitored phenotype parameters in comparison with any other tested RCS or parental strains. Mice of RCS CcS-11 showed shorter survival after T. b. brucei infection and strain CcS-9 exhibited higher eosinophil infiltration after L. major infection. For...
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Occurence and diversity of amphibian trypanosomes
Poloprutská, Klára ; Votýpka, Jan (advisor) ; Brzoňová, Jana (referee)
The genus Trypanosoma represents well-known flagellates of order Trypanosomatida and class Kinetoplastea, which includes over 500 described species parasitizing on all classes of vertebrates. However, the best known and economically and medically most important are mammalian trypanosomes, especially human ones, which cause serious diseases in the world: sleeping sickness in Africa and Chagas disease in Latin America. But trypanosomes may also be found in blood of birds, reptiles, fish and amphibians. And exactly on trypanosomes of amphibians, whose diversity is surprisingly vast, is this thesis focused. However, many studies concentrate only on morphological description, which may not be the best in order to determine species, which may lead to distortion of information e.g. about species' life cycle, prevalence or host specificity. This thesis points to some ambiguities, but also to some more reliable experimental or in some cases molecular evidence dealing with individual aspects of life of trypanosome of amphibians. It also summarizes representatives of aquatic and terrestrial invertebrate vectors of trypanosomes, among which leeches are considered to be the dominant vector in aquatic environment. Furthermore, some species of phlebotomes, mosquitoes and genus Corethrella are known to be...
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Genotype influence on development of infections caused by Trypanosomatidae in mouse
Šíma, Matyáš
Parasitic protists of genera Trypanosoma and Leishmania are members of Trypanosomatidae family. In our studies, we investigated genetic influence on infections caused by these parasites in a mouse model. These diseases are on genetic level controlled by quantitative trait loci (QTLs), when the resulting phenotype is controlled by set of genes with small individual effect. As a mouse model for mapping of QTLs controlling these infections, we used recombinant congenic strains (RCS). Each RCS carry unique set of 12.5% of the genome from donor parental strain on genetic background of other parental strain. For mapping of QTLs controlling infections caused by Trypanosoma brucei brucei (T. b. brucei) and Leishmania tropica (L. tropica) and eosinophil infiltration into inguinal lymph nodes after Leishmania major (L. major) infection, we used RCS from CcS/Dem series, where STS is donor strain and BALB/cHeA is strain of genetic background. First, it was necessary to find suitable model strains for mapping. In all three studies, we selected RCS, which exceeded range of monitored phenotype parameters in comparison with any other tested RCS or parental strains. Mice of RCS CcS-11 showed shorter survival after T. b. brucei infection and strain CcS-9 exhibited higher eosinophil infiltration after L. major infection. For...
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The Diverged Trypanosome MICOS Complex as a Hub for Mitochondrial Cristae Shaping and Protein Import
HELLER, Jiří
This work deals with MICOS, which stands for mitochondrial contact site and cristae organization system. Until now this multiprotein complex has been analyzed experimentally only in yeast and mammals, who belong to the supergroup Opisthokonta. Our study was done on the parasitic protist T. brucei, a member of the another supergroup called Excavata, which is very diverged from opisthokonts.Thus, it is the very first study done outside of Opisthokonta. This could be very useful in the future for a comparative analysis approach. Our results show that the MICOS complex in T. brucei is composed of 9 subunits, most of which are essential for normal growth. It is required for the maintenance of discoidal cristae that typify excavates such as kinetoplastids and euglenids and mediating the mitochondrial outer and inner membranes contacts. In addition, we discovered that the mitochondrial contact site and cristae organization system may participate in the intermembrane space protein import and help in the oxydative phosphorylation complex formation. It seems that this interesting complex is involved in even more cellular processes.
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Genotype influence on development of infections caused by Trypanosomatidae in mouse
Šíma, Matyáš ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Kolářová, Iva (referee)
Parasitic protists of genera Trypanosoma and Leishmania are members of Trypanosomatidae family. In our studies, we investigated genetic influence on infections caused by these parasites in a mouse model. These diseases are on genetic level controlled by quantitative trait loci (QTLs), when the resulting phenotype is controlled by set of genes with small individual effect. As a mouse model for mapping of QTLs controlling these infections, we used recombinant congenic strains (RCS). Each RCS carry unique set of 12.5% of the genome from donor parental strain on genetic background of other parental strain. For mapping of QTLs controlling infections caused by Trypanosoma brucei brucei (T. b. brucei) and Leishmania tropica (L. tropica) and eosinophil infiltration into inguinal lymph nodes after Leishmania major (L. major) infection, we used RCS from CcS/Dem series, where STS is donor strain and BALB/cHeA is strain of genetic background. First, it was necessary to find suitable model strains for mapping. In all three studies, we selected RCS, which exceeded range of monitored phenotype parameters in comparison with any other tested RCS or parental strains. Mice of RCS CcS-11 showed shorter survival after T. b. brucei infection and strain CcS-9 exhibited higher eosinophil infiltration after L. major infection. For...
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Trypanosomes of ungulates with emphasis on Europe
Brotánková, Anna ; Rádrová, Jana (advisor) ; Dvořák, Vít (referee)
Trypanosomes are veterinary and medically important parasites causing serious diseases and significant losses in livestock farming. Two subgenuses of trypanosomes were identified from ungulates in Europe. Trypanosoma evansi and T. equiperdum, flagellates of the subgenus Trypanozoon, could cause fatal infections to their hosts. Other Trypanosoma theileri, T. cervi, T. stefanskii, T. melophagium and T. theodori were discovered in European ungulates from the second subgenus Megatrypanum. These trypanosomes are common parasites in Europe, especially Trypanosoma theileri and T. cervi. On the other hand, T. evansi and T. equiperdum are occuring rather sporadically. Trypanosomes of the subgenus Megatrypanum are less significant because their lower medical and economical impact. They are generally apathogenic and so do not cause any clinical signs. Both morphological and phylogenetic informations of European trypanosomes are summarized in this work as well as details about their pathology, vectors and records of evidence in Europe.
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Use of RNAi and CRISPR systems in genetic modifications of parasitic protists
Kaiserová, Veronika ; Votýpka, Jan (advisor) ; Stojanovová, Darja (referee)
In organisms, RNA interference serves as a defence mechanism against foreign nucleic acids. RNAi has a negative effect on translation, via the binding of small non-coding molecules to the complementary region of mRNA, resulting in its degradation. CRISPR, a new method of genetic engineering, is based upon modulating genetic expression via creating double-stranded breaks in target DNA, aided by a ribonucleoprotein complex, consisting of the prokaryotic endonuclease Cas9 and sgRNA. Both of the aforementioned methods can be utilised in functional analysis of proteins and the characterisation of metabolic pathways in organisms of interest. This work summarises the current state of knowledge regarding RNAi and CRISPR and their use in genome editing of parasitic protists.
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Attachment of trypanosomatids in the insect vector.
Tichá, Lucie ; Myšková, Jitka (advisor) ; Leštinová, Tereza (referee)
Trypanosomatids are protozoan parasites known for its medical and economical significance. Leishmania, Trypanosoma, Endotrypanum and Phytomonas genera are dixenous parasites. Part of the life cycle takes place in the insect vector, where the parasites are attached using their flagella. Supraplyarian Leishmania differs in the binding method depending on the type of vector it uses for its transmission. The attachment is dependent on lipophosphoglycan (LPG) in a specific vector while in a permissive vector, the interaction is based on a different mechanism (LPG-independent). Attachment of T. cruzi in the posterior part of a digestive system of a hemipterous bugs appears to be necessary for metacyclogenesis. Similar strategy seems to be used by T. brucei which is attached in the salivary glands. The genera Endotrypanum and Phytomonas are not medically significant pathogens, thus their life cycles have not been profoundly researched. Endotrypanum, as well as Leishmania, develops in the digestive system of sand flies, thus the binding mechanism could be analogous. Phytomonas develops in the salivary glands of hemipterous bugs which denotes similarity with T. brucei. Based on the collected data, it is assumed that the binding mechanism of the Trypanosmonatids is generally based on the lectin-like protein...
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Mosquitoes as hosts and vectors of protozoa transmitted to birds
Fialová, Magdaléna ; Svobodová, Milena (advisor) ; Munclinger, Pavel (referee)
Mosquitoes belong to significant representatives of inscet which are particularly studied due to their ability to transmit pathogens (viruses, bacteria, protozoa, worms) in many cases causing serious illnesses. The hosts of these pathogens can be various animals including birds. In this study I have focused on protozoa (especially Plasmodium and Trypanosoma) transmitted by a mosquito. Concerning trypanosomes the mosquito is one of several possible vectors and up to now there have been named two trypanosomes transmitted by birds, namely Trypanosoma culicavium and Trypanosoma thomasbancrofti. In the case of the genus Plasmodium the mosquito is the only vector and there are many more species of the genus Plasmodium, which mosquito transmits between birds. Key words: vector, mosquito, host, bird, Trypanosoma, Plasmodium, infection
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