Evidence map›Paper›PMID 42011663›Full record

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.

Luisa Fernanda Gómez Londoño, Ana Camila Oliveira Souza, Brooks Burt, Sourav Das, Wenbo Ge, Vanessa Meza-Perez, Nathan P Wiederhold, Anang A Shelat, Christina A Cuomo, Jarrod R Fortwendel and 1 more

Abstract readComparative Study
In one paragraph

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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Luisa Fernanda Gómez LondoñoDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
Ana Camila Oliveira SouzaDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
Brooks BurtInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sourav DasDepartment of Chemical Biology and Therapeutics, St Jude Children's Research Hospital, Memphis, TN, USA.
Wenbo GeDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
Vanessa Meza-PerezDepartment of Host-Microbe Interactions, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-6828-5618
Nathan P WiederholdFungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-2225-5122
Anang A ShelatDepartment of Chemical Biology and Therapeutics, St Jude Children's Research Hospital, Memphis, TN, USA.
Christina A CuomoInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jarrod R FortwendelDepartment of Clinical Pharmacy and Translational Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.
P David RogersDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Non-cyp51A-mutation Mediated Triazole Resistance in Aspergillus fumigatusR01AI143197 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI FORTWENDEL, JARROD R., ROGERS, P. DAVID · 2020 to 2024
$3.3M
ALSACNIAID NIH HHS R01 AI143197NIH HHS P30CA021765NIH HHS R01 AI143197St. Jude Children's Research Hospital
6 · The paper itself

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.

Indexed as

Antifungal AgentsAspergillosisAspergillus fumigatusCytochrome P-450 Enzyme SystemDrug Resistance, FungalFungal ProteinsTriazolesGenetic VariationHumansMicrobial Sensitivity TestsPrevalenceUnited StatesAntifungal Agentscytochrome P-450 CYP51A, AspergillusCytochrome P-450 Enzyme SystemFungal ProteinsTriazoles

Identifiers

PMID42011663
PMCPMC13096733

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.