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Epidémiologie et mécanismes de résistance d'Aspergillus fumigatus aux antifongiques triazolés : focus sur les patients atteints de mucoviscidose / Epidemiology and mechanisms of resistance of Aspergillus fumigatus to triazole antifungal drugs : focus on patients with cystic fibrosisLavergne, Rose-Anne 12 July 2018 (has links)
Aspergillus fumigatus est un champignonfilamenteux opportuniste. / Aspergillus fumigatus is an opportunistic filamentous fungus, causing various clinical manifestations. The first-line treatment of aspergillosis is triazole antifungal drugs. The emergence of the resistance of A. fumigatus to this class of antifungals is a worrying and monitored phenomenon. The most frequent resistance mechanism involves 14 - demethylase, the target enzyme of azoles (encoded by the cyp51A gene). Two origins of resistance have been proposed: the first related to the selection of resistant isolates during long-term antifungal treatment and the second, an environmental origin following the use of demethylation inhibitor fungicides in the environment. Our work highlighted, for the first time, the presence of TR46/Y121F/T289A isolates in France. Furthermore, the exploration of the genotypic link between clinical and environmental isolates carrying the TR46/Y121F/T289A alteration validated the hypothesis of the environmental origin of azole resistance. A prospective one-year study in cystic fibrosis patients confirmed a relatively high level prevalence of resistance together with the presence of wild-type cyp51A resistant isolates. The latter isolates were investigated for yet unidentified resistance mechanisms, initially analysing the sterol biosynthesis pathway. This work contributes to a better knowledge of the epidemiology and resistance mechanisms of A. fumigatus to azole drugs.
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