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Books on Demand Stabilität hoher Fluorchinolonresistenz bei Enterobakterien ohne Selektionsdruck

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Description

Dissertation / Doktorarbeit, die am 31.08.2001 erfolgreich an einer Universität in Deutschland im Fachbereich Medizinische Fakultät eingereicht wurde. Beide Auszeichnungen wurden auf Vorschlag der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. verliehen. Der Aventis Travel Award 2001 war ein Stipendium zum Besuch der 40th ICAAC, Toronto, Kanada, gestiftet von Aventis Pharma GmbH. Zusammenfassung: Als Präventivmaßnahme zur Eindämmung der Resistenz gegen Antibiotika wurde 1995 von der WHO vorgeschlagen, den Antibiotikaeinsatz weltweit zu reduzieren, um damit der Selektion von resistenten Bakterien entgegenzuwirken. Grundlage dieser WHO-Empfehlung ist die Annahme, daß die Fitness von Antibiotika-resistenten Mutanten im Vergleich zu sensitiven Stämmen signifikant verringert ist und diese daher beim Wegfall des Selektionsdrucks die resistenten Stämme verdrängen. Die klinische Fluorchinolonresistenz bei Escherichia coli ist eine Folge der Akkumulation von Mutationen in den Genen der Zielstrukturen Gyrase und Topoisomerase IV. Des weiteren spielt oftmals eine Veränderung der mar-regulierten Expression von Porinen und Effluxpumpen eine Rolle. Bei in vitro selektierten E. coli konnte, im Zusammenhang mit der Resistenzentwicklung, eine erhebliche Verminderung der Fitness festgestellt werden. Neben einer verlängerten Generationszeit, wurde die Abnahme des negativen Superspiralisierungsgrads der DNA, sowie der Verlust der Typ 1 Fimbrienexpression festgestellt. Dies steht im Gegensatz zu den Befunden bei klinischen Isolaten. Um die Frage zu klären, ob der Fitnessverlust der Bakterien die WHO-Annahme bestätigt, oder, ob eventuell kompensatorische Mutationen diesen Fitnessverlust ausgleichen können, wurde in dieser Arbeit ein Fitness-Kompensationsexperiment durchgeführt. Es bestand darin, die Ciprofloxacin-resistenten Zellen über 300 Generationen ohne Antibiotikaselektionsdruck in vitro zu kultivieren, dabei setzten sich die

Product Specifications

Format
paperback
Domain
Amazon UK
Release Date
01 January 2001
Listed Since
06 February 2009

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