Genetic Analysis Using an Isogenic Mating Pair of Identifies Azole Resistance Genes and Lack of Locus’s Role in Virulence

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Invasive aspergillosis (IA) caused by Aspergillus fumigatus is increasing due to medical interventions that suppress the ability of patients’ immune systems to control infections. These invasive lung infections are difficult to diagnose and consequently treatment is frequently not started promptly. Some controversy surrounds the role of mating type in virulence of A. fumigatus and the emergence of azole resistant strains has posed difficult challenges for clinical management of IA. We generated nearly identical A. fumigatus strains with opposite mating types that allowed us to test whether different mating types have different virulence profiles. We found no difference in virulence in three different animal models, which suggests that mating type does not influence virulence. We also took advantage of the essentially identical genomes of both strains to apply classical genetic approaches combined with genomics technologies to identify A. fumigatus genes that contribute to azole resistance. We performed genetic crosses of azole sensitive with azole resistant strains and analyzed the resistance status and genome composition of the offspring. Using this approach we cataloged several genes that were not previously associated with azole resistance. This information will be valuable for finding ways to manage azole resistance in IA patients.

Vyšlo v časopise: Genetic Analysis Using an Isogenic Mating Pair of Identifies Azole Resistance Genes and Lack of Locus’s Role in Virulence. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004834
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004834

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