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Mechanisms of metronidazole resistance in bacteria and anaerobic eukaryotes
Pilařová, Kateřina ; Hrdý, Ivan (advisor) ; Kulda, Jaroslav (referee)
This bachelor thesis tries to describe mechanisms of resistance in different groups of organisms, where metronidazole is used for treatment. These organisms are bacteria (genus Bacteroides, Helicobacter, Clostridium) as well as anaerobic eukaryota (genus Trichomonas, Tritrichomonas, Entamoeba, Giardia). It is important, that metronidazole acts selectively only on cells living in anaerobic or microaerophilic environments. Metronidazole enters the cell by passive diffusion and is subsequently reduced to cytotoxic intermediate which damages the cell at different levels. Metronidazole can also enter the cell with aerobic metabolism, also the reduction can occur, but the eventual radical is then thanks to oxygen transformed back to metronidazole in the process called futile cycling. Oxygen then forms superoxide, O2-. Organisms with aerobic or microaerophilic metabolism cannot detoxify nitroradical with oxygen, so they developed other ways how they protect themselves against the harmful effects of nitroradicals. Sensitivity of these patogens to metronidazole correlates with the changes of their enzymatic constitution. Perhaps the most basic mechanism how the patogens combat metronidazole is the prevention of reduction of the drug. The way how the organisms prevent reduction differs between species. There is a...
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Mechanisms of metronidazole resistance in bacteria and anaerobic eukaryotes
Pilařová, Kateřina ; Kulda, Jaroslav (referee) ; Hrdý, Ivan (advisor)
This bachelor thesis tries to describe mechanisms of resistance in different groups of organisms, where metronidazole is used for treatment. These organisms are bacteria (genus Bacteroides, Helicobacter, Clostridium) as well as anaerobic eukaryota (genus Trichomonas, Tritrichomonas, Entamoeba, Giardia). It is important, that metronidazole acts selectively only on cells living in anaerobic or microaerophilic environments. Metronidazole enters the cell by passive diffusion and is subsequently reduced to cytotoxic intermediate which damages the cell at different levels. Metronidazole can also enter the cell with aerobic metabolism, also the reduction can occur, but the eventual radical is then thanks to oxygen transformed back to metronidazole in the process called futile cycling. Oxygen then forms superoxide, O2-. Organisms with aerobic or microaerophilic metabolism cannot detoxify nitroradical with oxygen, so they developed other ways how they protect themselves against the harmful effects of nitroradicals. Sensitivity of these patogens to metronidazole correlates with the changes of their enzymatic constitution. Perhaps the most basic mechanism how the patogens combat metronidazole is the prevention of reduction of the drug. The way how the organisms prevent reduction differs between species. There is a...
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