Abstract
Aspergillus fumigatus is a ubiquitous saprophytic mold and a major pathogen in immunocompromised patients. The effectiveness of triazole compounds, the A. fumigatus first line treatment, is being threatened by a rapid and global emergence of azole resistance. Whole genome sequencing (WGS) has emerged as an invaluable tool for the analysis of genetic differences between A. fumigatus strains, their genetic background, and antifungal resistance development. Although WGS analyses can provide a valuable amount of novel information, there are some limitations that should be considered. These analyses, based on genome-wide comparative data and single nucleotide variant (SNV) calling, are dependent on the quality of sequencing, assembling, the variant calling criteria, as well as on the suitable selection of the reference genome, which must be genetically close to the genomes included in the analysis. In this study, 28 A. fumigatus genomes sequenced in-house and 73 available in public data bases have been analyzed. All genomes were distributed in four clusters and showed a variable number of SNVs depending on the genome used as reference (Af293 or A1163). Each reference genome belonged to a different cluster. The results highlighted the importance of choosing the most suitable A. fumigatus reference genome to avoid misleading conclusions.
Highlights
Aspergillus fumigatus is a saprophytic filamentous fungus and the principal causative agent of human aspergillosis [1,2]
The isolates were identified at the species level and the azole resistance mechanism was analyzed by PCR amplification and sequencing of the cyp51A gene and its promoter as explained in Materials and Methods section
The azole susceptibility profile was determined based on the known cyp51A modifications detected by whole genome sequencing (WGS) analysis
Summary
Aspergillus fumigatus is a saprophytic filamentous fungus and the principal causative agent of human aspergillosis [1,2]. There are many types of diseases caused by A. fumigatus and their symptoms vary according to the site of infection and host health condition. This species causes invasive infections, such as invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised or immunosuppressed patients [3,4,5]. Genomics and whole genome sequencing (WGS) have emerged as useful tools to greatly enhance knowledge and understanding of infectious diseases and clinical microbiology [7,8,9,10] In this context, genome-wide sequencing using high throughput sequencing (HTS) together with alignment comparison analysis has been described as
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