PMID:15504870 In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance

[MPiovesana]

Curated by @MPiovesana https://canto.phi-base.org/curs/7700f6fcef8b7f8e

[MPiovesana]

In this paper, authors generate itraconazole-resistant mutants by directed evolution of the wild type strain CEA17 of Aspergillus fumigatus. A number of mutants are isolated, which are found to harbour several point mutations in the CYP51A and CYP51B genes. Authors perform a gene replacement experiment to confirm the involvement of CYP51A mutations in itraconazole resistant, and find that only two of the mutations (N22D and M220I) chance the susceptibility of CEA17 to the fungicide. This result is only mentioned in the text followed by (data not shown). As only two of these mutations were confirmed to be involved with the chemical resistance phenotype, I decided to only curate these two alleles as transformants in the CEA17 background.

[MPiovesana]

Uniprot ID: CYP51A of A. fumigatus was promptly identified in Uniprot (Q4WNT5).

Strain: CEA17 was selected.

[MPiovesana]

Genotype creation: the following genotypes were created:

cyp51A transformant(H10-1-50A-cyp51A(N22D)) = transformant allele; cyp51A allele from strain H10-1-50A harbouring N22D mutation;

cyp51A transformant(H10-2-50A-cyp51A(M220I)) = transformant allele; cyp51A allele from strain H10-2-50A harbouring M220I mutation

Cyp51Adelta was added to the background of both genotypes.

[MPiovesana]

Genotype annotation: both genotypes were annotated with PHIPO term resistance to itraconazole. No other phenotypical characteristic for the transformant lines is described in the study.

[MPiovesana]

Curation completed pending review.

[CuzickA]

AE alteration_in _archetype

N22D; Cyp51A; ASPEFU M220I; Cyp51A; ASPEFU

Questions for Nichola

Are these correct? I could not find info on Cyp51A in your S file. I found the above information from Table 2 in Mair et al 2016.

[CuzickA]

Approving session once AE checked. Closing ticket.

[CuzickA]

Are these correct? I could not find info on Cyp51A in your S file. I found the above information from Table 2 in Mair et al 2016. YES this is correct

[CuzickA]

AE alteration_in _archetype checked by Nichola. Session now approved.