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Diplomarbeit aus dem Jahr 2011 im Fachbereich Biologie - Mikrobiologie, Molekularbiologie, Note: 1, Universität Wien, Sprache: Deutsch, Abstract: The protozoan parasite Trichomonas vaginalis is the causative agent of trichomonosiswhich is - with more than 170 million new cases each year - the most prevalentnon-viral sexually transmitted disease (STD) worldwide. Although trichomonosis isnot a primarily lethal disease, the clinical picture can include severe urogenitalinflammations. Chronic infections have been associated with cervical/prostate cancerand a predisposition of HIV infections. In case of pregnancy, chronic infections canalso lead to preterm delivery and low birth weight. For more than 50 years,metronidazole, a nitroimidazole antibiotic, has been in use for the treatment oftrichomonosis. It is applied orally and although it is mostly compliant, it can haveserious side effects. It is also not applicable for pregnant women due to its ability topass the placenta. Furthermore, an increasing number of emerging metronidazoleresistantT. vaginalis strains has lead to more treatment failures in the last few years.To this day, however, there is no effective alternative drug against trichomonosisavailable.Pentamycin is a polyene antimycotic and has been in use in the treatment ofcandidiasis, in preliminary studies it also turned out to be effective againsttrichomonads.The aim of this study was to evaluate the efficacy of pentamycin against T. vaginalisand the ability to develop resistances in vitro. For these purposes, the dose-effectrelationship between pentamycin and four differently metronidazole-sensitive T.vaginalis strains was investigated. Moreover, the protein composition before and afterthe treatment was compared. To induce resistance, strains were treated withsublethal concentrations of pentamycin within a time of six months.It could be shown that pentamycin is highly effective against T. vaginalis. A 100%eradication of trichomonads was reached with a concentration of 15 ;g/ml and anincubation time of 1h. All four differently metronidazole-sensitive strains showedalmost the same sensitivity to pentamycin. The comparison of the protein profiles ofuntreated and treated cells analysed by SDS-PAGE showed that the mode of actionof pentamycin is based on an interaction and subsequent damage of the cellmembrane which consequently leads to total lysis and death of the cell. [...]
