Genomic epidemiology identifies azole resistance due to TR34/L98H in European aspergillus fumigatus causing COVID-19-associated pulmonary aspergillosis
Aspergillus fumigatus has been found to coinfect patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA A. fumigatus isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider A. fumigatus population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% (n = 3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected.
Funding
NERC (nos. NE/P001165/1 and NE/P000916/1)
UK Medical Research Council (MRC) (no. MR/R015600/1)
Wellcome Trust (no. 219551/Z/19/Z)
CIFAR Fungal Kingdoms Program
History
Data Availability Statement
All raw reads have been submitted to the European Nucleotide Archive (ENA) under Project Accession no. PRJEB60964. Two hundred and twenty-one raw reads of clinical non-CAPA and environmental A. fumigatus isolates have also been deposited under project accession no. PRJEB27135. The raw short reads of four German CAPA isolates have previously been deposited to the NCBI’s GenBank database under BioProject accession no. PRJNA673120.Comments
The original article is available at https://www.mdpi.com/Published Citation
Simmons BC, et al. Genomic epidemiology identifies azole resistance due to TR34/L98H in European aspergillus fumigatus causing COVID19-associated pulmonary aspergillosis. J Fungi (Basel). 2023;9(11):1104.Publication Date
13 November 2023External DOI
PubMed ID
37998909Department/Unit
- Clinical Microbiology
Publisher
MDPIVersion
- Published Version (Version of Record)