Abstracts (first author)
Azole resistance in Aspergillus fumigatus: condition-dependent mutations for resistance
Azole resistance in Aspergillus fumigatus: condition-dependent mutations for resistance and compensatory evolution Jianhua Zhang, Sijmen E. Schoustra, Marijke Slakhorst, Bertha Koopmanschap, Alfons J. M. Debets, Paul E. Verweij, Bas J. Zwaan Laboratory of Genetics, Wageningen University; Department of Medical Microbiology, Radboud University, Nijmegen. Abstract: Azole resistance is an emerging problem in the saprophytic mold Aspergillus fumigatus, which is involved in the vast majority of invasive infections in the human lung. Resistance is widespread in the Netherlands with a prevalence of 5.3%. The majority of highly resistant mutants have undergone two mutational events: an insert in the promoter region (tandem repeat TR34) and a point mutation in the structural region of the cyp51 gene (L98H). The occurrence of two mutational events at the same time is highly unlikely to happen by chance. To prevent and stop the spread of azole resistant strains, understanding the condition-dependent occurrence of TR34/L98H resistance and potential compensatory mutations for reducing the cost of resistance in the filamentous fungus A. fumigatus is crucial. We hypothesise that a combination of different modes of reproduction of the fungus facilitates the combination of the cyp51 point mutation with the tandem repeat into one background. In addition, mutagenic and recombinogenic environmental conditions may play an important role in the development of resistance. We present data of our study on the dynamics of TR34/L98H resistance by experimental evolution in the laboratory under various environmental conditions in combination with variation in the life.