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Mechanisms and aplications of macromolecule translocation across membranes of eukaryotic cells by bacterial toxins
Poledňák, Jan ; Fišer, Radovan (advisor) ; Žáčková Suchanová, Jiřina (referee)
Toxin translocation across the cytoplasmic membrane of the eukaryotic cell is a potent virulence factor of bacteria causing disease to eukaryotic organisms. Toxins translocate their domains responsible for the toxic activity inside the cell or create pores in cell membrane allowing the transmembrane traffic of ions, DNA, RNA or proteins. Knowledge of the toxin translocation process enables to characterize the mechanism and also the properties of the pore-forming toxin. Some of these toxins have been described in such a detail that were changed using site-directed mutagenesis and can serve as tools for characterization of the translocated molecules. One of such examples is the transfer of nucleotides or the whole nucleic acid molecules across the membrane through the pore of S. aureus α-hemolysine. Nowadays, this application is commercially used for DNA sequencing. Keywords: translocation, bacterial toxins, plasmatic membrane, nanopore sequencing
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The role of posttranslational modifications in action of bacterial toxins
Hudáčková, Kristýna ; Mašín, Jiří (advisor) ; Večerek, Branislav (referee)
Posttranslational modifications of proteins are a widespread mechanisms used by both prokaryotic and eukaryotic cells for increase the diversity of the proteome by the addition of functional groups, proteins, proteolytic cleavage of regulatory subunits, or degradation of entire proteins. These modifications include for example phosphorylation, glycosylation, acetylation, lipidation, ubiquitination or proteolysis and affect almost all aspects of cell biology and pathogenesis. Toxins produced by microorganisms are important virulence factors. Many of these bacterial toxins use posttranslational modification for their activation, as for example listeriolysin O, toxins of Bacillus anthracis or clostridial toxins. Large group of bacterial toxins activated by fatty acid are RTX (from Repeats-in-ToXin) toxins of Gram-negative pathogens, including Bordetella pertussis adenylate cyclase toxin or α-hemolysin secreted by uropathogenic Escherichia coli.
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Mechanism of action of bacterial toxins elevating the cAMP in host cells
Lepesheva, Anna ; Mašín, Jiří (advisor) ; Petráčková, Denisa (referee)
Cyclic adenosine monophosphate (cAMP) is an universal second messenger that regulates a large number of molecular mechanisms inside the eukaryotic cell. The level of synthesized cAMP is tightly regulated by endogenous adenylatecyclase (AC), and therefore this enzyme is often a target for various bacterial toxins. To manipulate intracellular cAMP levels in a target cell, bacteria have developed two different strategies for their toxins. Bordetella pertussis adenylate cyclase toxin (CyaA), Bacillus anthracis edema factor (EF) and Pseudomonas aeruginosa exotoxinY have in their structure an enzymatic AC domain which is activated by an intracellular cofactor and has several times higher activity than the eukaryotic AC enzyme itself. Other toxins, such as Bordetella pertussis pertussis toxin (PT), Vibrio cholerae cholera toxin (CT), and Escherichia coli heat labile toxin use ADP-ribosylation reaction of AC-coupled heterotrimeric G proteins to increase its activity and uncontrolled cAMP production. This work presents a literature search with accent on the molecular mechanism of interaction of these toxins with the target cell. Keywords: bacterial pathogens, virulence factors, intracellular cAMP elevation, bacterial toxins, adenylatecyclase (adenylylcyclase), Bordetella pertussis, Vibrio cholerae,...
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Mechanisms and aplications of macromolecule translocation across membranes of eukaryotic cells by bacterial toxins
Poledňák, Jan ; Fišer, Radovan (advisor) ; Žáčková Suchanová, Jiřina (referee)
Toxin translocation across the cytoplasmic membrane of the eukaryotic cell is a potent virulence factor of bacteria causing disease to eukaryotic organisms. Toxins translocate their domains responsible for the toxic activity inside the cell or create pores in cell membrane allowing the transmembrane traffic of ions, DNA, RNA or proteins. Knowledge of the toxin translocation process enables to characterize the mechanism and also the properties of the pore-forming toxin. Some of these toxins have been described in such a detail that were changed using site-directed mutagenesis and can serve as tools for characterization of the translocated molecules. One of such examples is the transfer of nucleotides or the whole nucleic acid molecules across the membrane through the pore of S. aureus α-hemolysine. Nowadays, this application is commercially used for DNA sequencing. Keywords: translocation, bacterial toxins, plasmatic membrane, nanopore sequencing
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Mechanisms and aplications of macromolecule translocation across membranes of eukaryotic cells by bacterial toxins
Poledňák, Jan ; Fišer, Radovan (advisor) ; Žáčková Suchanová, Jiřina (referee)
The bacterial protein toxins endowed with the ability to translocate across the plasmatic membrane are often crucial virulence factors of pathogenic bacteria invading eukaryotic organisms. These toxins translocate either their own protein domains carrying toxic activity or can form pores transferring other substances like small ions, DNA, RNA or proteins. By observing the translocation of these molecules together with other artificially prepared agents on synthetic membranes it allows detailed understanding of mode of action of individual pore-forming toxins. Some of the toxins were actually described in such a detail that can serve as tools for drug delivery or characterization of new translocated molecules. One of such examples is the transfer of nucleotides or the whole nucleic acid molecules across the membrane pore of S. aureus α-hemolysine. Nowadays, this application is commercially used for DNA sequencing. Keywords: translocation, bacterial toxins, plasmatic membrane, nanopore sequencing
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