ArticleThe Journal of antimicrobial chemotherapy2026
Prevalence of cyp51A variants in a US collection of Aspergillus fumigatus clinical isolates and comparative analysis of their contribution to triazole antifungal resistance.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo determine the frequency of cyp51A variants among a contemporary collection of triazole-resistant Aspergillus fumigatus clinical isolates from the USA and compare their specific contribution to reduced triazole susceptibility.
methodsThe genomes of 87 isolates with decreased susceptibility to at least one mould-active triazole antifungal collected between 2007 and 2020 were sequenced. The cyp51A variants were identified and genetically introduced into a cyp51A-null strain. Antifungal susceptibilities for the mould-active triazole antifungals were determined following CLSI guidelines, and variant positions were mapped after protein homology modelling.
resultsMost clinical isolates (60%) carried one of 15 variants that reduced susceptibilities to short-chain (G448S, Y121F, TR46/Y121F/T289A and TR46/Y121F/T289A/N512), long-chain (P216L, F219S and substitutions in the G54 and M220 residues) or multiple (TR34/L98H and TR34/L98H/S297T/F495I) triazoles. While TR34/L98H and TR46/Y121F/T289A were among the most common variants affecting susceptibility, occurring in 13 and 9 isolates, respectively, variants exclusively affecting the coding region and influencing susceptibility were most common, occurring in 31 isolates. A total of 14 isolates (16%) exhibited reduced susceptibility that could not be explained by variants in any known resistance determinants (cyp51A, hmg1 or hapE).
conclusionsOur findings demonstrate the range of mutations affecting triazole resistance among US isolates and provide a much-needed side-by-side comparison of the impact of these variants on the most currently used mould-active triazole antifungals. Moreover, they underscore the extent to which triazole resistance remains unexplained by known genetic determinants and the need for further discovery.
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