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Cryptococcus neoformans virulence factors
Bauer, Martin ; Kuthan, Martin (advisor) ; Abrhámová, Kateřina (referee)
Cryptococcus neoformans is an opportunistic pathogenic yeast causing around 600 000 deaths annually. Its ability to cause a chronic infection is given by multiple virulence factors, which include the ability to grow in high temperature, polysaccharide capsule, oxidative stress tolerance and the expression of surface proteins. Unusual and resistant titan cells, which develop through the process of titanization, and the process of phenotypic switching can also be included. Despite intensive research, these virulence factors are yet to be fully described. Inducing factors of titan cells and participating signalling pathways are known. However, a complete model of titanization does not yet exist. So far, the mechanism of phenotypic switching is also unknown. In this work the current knowledge of virulence factors of C. neoformans is presented and summarised.
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Phenotypic switching and cell differentiation in yeast Cryptococcus neoformans
Bauer, Martin ; Kuthan, Martin (advisor) ; Abrhámová, Kateřina (referee)
Cryptococcus neoformans is an opportunistic pathogenic yeast causing around 600 000 deaths annually. Its ability to cause a chronic infection is given by the emergence of different morfotypes. These morphotypes differ in cell structures and mechanisms (virulence factors) which have an influence on the resistance to stress factors encountered in the host. This work first describes molecular mechanisms of formation of these virulence factors. Next, it presents morphotypes occurring during infection and the hypovirulent pseudohyphal morphotype. However, this morphotype is interesting because of a modification in the signalisation leading to its manifestation. Finally, described signalling pathways present possible ways of regulating the virulence factors, and so the manifestation of different morphotypes. Understanding these signalling pathways could ultimately lead to improving the development of new drugs, given that Cryptococcus neoformans is highly resistant to the existing ones. Keywords: Cryptococcus neoformans, phenotypic switching, titan cells, cell differentiation, virulence, Vad1, Rim101, Usv101, RAM
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Studies of S. cerevisiae BR-S strain with deletion of SIR2 gene
Novotná, Pavla ; Kuthan, Martin (advisor) ; Pichová, Iva (referee)
Yeasts are unicellular eukaryotic microorganisms, capable of forming of organised multicellular communities, the colonies. Many yeast strains possess a characteristic colony morphology under defined living conditions. Another feature typical for many feral and pathogenic yeast strains is the ability to switch their morphotype. This phenomenon, called the phenotypic switching, contributes to a rapid adaptation to the changing harmful environment and is often connected with changes of the stress resistance or with the changes of virulence of pathogenic yeasts. Phenotypic switching can be observed even in non-pathogenic yeast Saccharomyces cerevisiae. The strain BR-F, isolated from nature, switches under laboratory conditions from fluffy to smooth morphology of the strain BR-S. This phenotypic switch is accompanied by broad changes in the phenotype. Transcriptome analyses of the strains BR-F and BR-S have shown, among others, changes in expression of the subtelomeric genes that are under control of the histone acetylases and deacetylases. My work was aimed to the histone deacetylase Sir2p, which could influence the phenotypic switching in Saccharomyces cerevisiae. The sir2 deletion mutant of the strain BR-S, prepared in our laboratory, was used for my studies. The results show, that the strain BR-S...
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Study of the function of selected genes in the colonies of wild yeast strains
Tarabová, Eva ; Kuthan, Martin (advisor) ; Heidingsfeld, Olga (referee)
Saccharomyces cerevisiae strains isolated from the wild are able to exhibit multicellular social behaviour and to form complex structured colonies resembling in many properties highly resistant biofilms of pathogenic yeasts. The capability of phenotypic variability, i.e. high frequency transition between two or more different phenotypes, is another feature typical for the wild yeast strains. Such phenotypic changes are in case of pathogenic yeast often connected with changes in virulence and resistance to stress and antifungal treatment. Long-term cultivation of the wild yeast strains under laboratory conditions leads to their domestication, i.e. transition to smooth colonies and loss of some features typical for structured colonies. This process is, similarly to phenotypic switching, accompanied by significant changes in gene expression and global change of colony lifestyle. Mechanisms underlying yeast phenotypic transitions are ascribed to epigenetic regulation of gene expression via transcriptional silencing conferred by histone deacetylases. This work deals with the study of such mechanisms using knock-outs of selected genes with putative function in formation of structured colonies in wild and domesticated strains. The achieved results show, that NAD+-dependent histone deacetylase Sir2p influences...
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