Antimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, we performed a thorough manual curation of published AMR mutations in fungal pathogens to produce the FungAMR reference dataset. A total of 462 papers were curated, leading to 54,666 mutation entries all classified with the degree of evidence that supports their role in resistance. FungAMR covers 92 species, 202 genes and 184 drugs. We combined variant effect predictors with FungAMR resistance mutations and showed that these tools could be used to help predict the potential impact of mutations on AMR. Additionally, a comparative analysis among species revealed a high level of convergence in the molecular basis of resistance, revealing some potentially universal resistance mutations. The analysis also showed that a significant number of resistance mutations lead to cross-resistance within antifungals of a class, as well as between classes for certain mutated genes. The acquisition of fungal resistance in the clinic and the field is an urging concern. Finally, we provide a computational tool, ChroQueTas, that leverages FungAMR to screen fungal genomes for AMR mutations. These resources are anticipated to have great utility for researchers in the fight against antifungal resistance.
The FungAMR compendium contains 54,666 curated entries across 184 drugs (including 104 antifungals) for 92 fungal species and contains missense mutations as well as other genomic changes such as copy-number variations and nonsense mutations. Additional metadata, including sources for the original data, are available in the GitHub spreadsheet.
If you use these data, please cite: Bédard et al. 2024. FungAMR: A comprehensive portrait of antimicrobial resistance mutations in fungi. bioRxiv 2024.10.07.617009.
Confidence score: a positive confidence score denotes mutations reported to confer resistance, while a negative confidence score relates to mutations reported in susceptible strains. A low positive confidence score indicates that the evidence for the contribution of the mutation to resistance is strong, with 1 being the strongest and 8 being the weakest. Similarly for negative scores, the evidence of susceptibility is stronger for -1 than -8. Full details are available at GitHub. Ortholog group: name of a protein orthologous or homologous to the listed protein (for data standardization). Resistance & Sensitivity evidence: the lowest positive (resistance) or lowest negative (sensitivity) confidence score assigned to the mutation in the FungAMR database. Orthologous mutations & residues: curated group numbers assigned to orthologous positions in different species based on multiple sequence alignments. Orthologous mutations share the same alternate amino acid, whereas orthologous residues can have any amino acid at the position.
| Reference | Gene or Protein name | Species | Drug | Mutation | Confidence score | Ortholog group | Resistance evidence | Sensitivity evidence | Orthologous mutation group | Orthologous residues group |
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