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Motility and virulence of bacterial pathogens in patients with cystic fibrosis
Benešová, Nikol ; Melter, Oto (advisor) ; Smělíková, Eva (referee)
Cystic fibrosis is an autosomal recessive disease that mainly effects the Europoid race. The disease is caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene. This gene encodes the formation of chloride channel proteins. The disease leads to the formation of highly viscous secretions from the exocrine glands. The most commonly affected organ is the lung, which accumulates mucus and bacteria. Bacteria that colonize the lungs of patients with cystic fibrosis are exposed to many stress factors such as large amounts of mucus, oxidative stress, antibiotics and immune system of the host. That leads to the selection of mutants that are better adapted to the environment of the lungs. In acute infection, one of the important virulence factors for bacteria is their motility. Motility is provided by flagella and allows the bacterium to move to sites with higher nutrient content and to colonise different parts of the lung. In chronic infection, we can see changes in the genotype and phenotype of bacteria. Nonmotile mutants are selected because they activate the immune system less than motile bacteria, that helps in the persistence of bacteria in the lungs. Chronic infections lead to a higher mortality rate. The aim of this bachelor's thesis is to compare the motility of bacteria...
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Mechanisms of bacterial persistence and clinical significance
Smělíková, Eva ; Melter, Oto (advisor) ; Pinkas, Dominik (referee)
Persistent bacteria, shortly persisters, are cells that are characterized by their tolerance to antibiotics without containing resistance genes. These are not resistant bacteria, because resistant bacteria are determined by genetic code. Persisters are indistinguishable from other antibiotic sensitive bacteria, and they are rather transient phenotypic subpopulations. Probably all types of bacteria can create a persistent stage, the ability is not species-bound and persistence has been described in a number of bacterial species. The reason for the formation of persistence may be sudden stress, then it is induced formation, or the reason may be an insurance for the future, then we call it stochastic phenotypic variability. Then a variety of phenotypes of different subpopulations within a genetically uniform population can be distinguished. They differ in growth properties and tolerance to antibiotics. Bet-hedging strategy is a hypothesis that describes persistence as insurance against the risk of external fluctuations. During stress an alarmon guanosine tetraphosphate or guanosine pentaphosphate is accumulated to alert the cell to unfavorable conditions and it initiates transition to a more tolerant state. The existence of these tolerant subpopulations is important in recurrent diseases because small...
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Colistin resistance in clinically important Enterobacteriaceae
Smělíková, Eva ; Tkadlec, Jan (advisor) ; Ježek, Petr (referee)
Colistin is a last-resort antibiotic used to treat serious infections caused by Enterobacteriaceae and other multidrug resistant gram-negative bacteria. Recently discovered plasmid-borne colistin resistance, mediated by the mcr genes, poses a serious risk to colistin therapy. The aim of this diploma thesis was to map the occurrence of Enterobacteriaceae carrying the mcr-1 to 8 genes in hospitalized patients, travellers, prospective colistin-resistant clinical isolates and in a retrospective collection of Enterobacteriaceae using a combination of selective cultivation and qPCR. Isolates with a detected mcr gene were characterized by Whole-Genome Sequencing. The localization of mcr genes was determined and other resistance genes and plasmids were identified. Furthermore, the physiological profile of selected colistin- resistant Escherichia coli isolates was characterized. In the presence of a subinhibitory amount of colistin, a strain carrying the mcr-1 gene may be favored. Later, the mcr-9 gene was described and its occurence was subsequently tested retrospectively. Enterobacter spp. isolates carrying the mcr-9 gene were mostly colistin-sensitive but, in some cases, resistance was induced after exposure to sublethal doses of colistin. The results of the study show that the incidence of plasmid-mediated...
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Mechanisms of bacterial persistence and clinical significance
Smělíková, Eva ; Melter, Oto (advisor) ; Pinkas, Dominik (referee)
Persistent bacteria, shortly persisters, are cells that are characterized by their tolerance to antibiotics without containing resistance genes. These are not resistant bacteria, because resistant bacteria are determined by genetic code. Persisters are indistinguishable from other antibiotic sensitive bacteria, and they are rather transient phenotypic subpopulations. Probably all types of bacteria can create a persistent stage, the ability is not species-bound and persistence has been described in a number of bacterial species. The reason for the formation of persistence may be sudden stress, then it is induced formation, or the reason may be an insurance for the future, then we call it stochastic phenotypic variability. Then a variety of phenotypes of different subpopulations within a genetically uniform population can be distinguished. They differ in growth properties and tolerance to antibiotics. Bet-hedging strategy is a hypothesis that describes persistence as insurance against the risk of external fluctuations. During stress an alarmon guanosine tetraphosphate or guanosine pentaphosphate is accumulated to alert the cell to unfavorable conditions and it initiates transition to a more tolerant state. The existence of these tolerant subpopulations is important in recurrent diseases because small...
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