Evidence map›Paper›PMID 41649269›Full record

ArticlemBio2026

Mutations in ERG11, TAC1B, and CDR1 reduce fluconazole accumulation in drug-resistant Candidozyma auris isolates.

Brooke D Esquivel, Amanda Santos, Jeffrey M Rybak, Darian J Santana, P David Rogers, Theodore C White

Abstract read
In one paragraph

Article in mBio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Brooke D EsquivelDivision of Biological and Biomedical Systems, School of Science and Engineering, University of Missouri-Kansas City, Kansas City, Missouri, USA.ORCID 0000-0001-7328-4057
Amanda SantosMycotic Diseases Branch, NCEZID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID 0000-0002-5577-4498
Jeffrey M RybakDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-9317-0935
Darian J SantanaDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
P David RogersDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-4401-0679
Theodore C WhiteDivision of Biological and Biomedical Systems, School of Science and Engineering, University of Missouri-Kansas City, Kansas City, Missouri, USA.ORCID 0000-0003-3229-1378

Funding

Novel Azole Resistance Mechanisms in Candida albicansR01AI058145 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROGERS, P. DAVID · 2005 to 2021
$5.8M
Upc2A: A Central Regulator and "Achilles' Heel" of Fluconazole Resistance in Candida glabrataR01AI131620 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROGERS, P. DAVID · 2017 to 2021
$2.7M
Training in the Design and Development of Infectious Disease TherapeuticsT32AI106700 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Richard E. Lee · 2015 to 2026
$2.1M
NIAID NIH HHS R01 AI058145NIAID NIH HHS R01 AI131620NIAID NIH HHS T32 AI106700
6 · The paper itself

Abstract

Fluconazole (FLC)-resistant Candidozyma auris isolates have reduced drug accumulation compared to azole-susceptible isolates. Of 119 C. auris isolates, 83 out of 87 resistant isolates (~95%) had extremely low fluconazole uptake, whereas 30 out of 32 susceptible isolates (~93%) had high fluconazole uptake. In search of a genetic explanation for this phenomenon, we compared metadata for TAC1B and CDR1 single-nucleotide polymorphisms (SNPs) and found overlap with many but not all isolates that are FLC resistant. We found that CDR1 mutations are common in resistant isolates from Clade 1, and TAC1B mutations are commonly found in resistant isolates from clades 1 and 3. There is clearly an association between FLC resistance and certain CDR1 and TAC1B polymorphisms, but mutations in these genes do not account for all mechanisms of resistance in this species and do not account for the difference in FLC accumulation. However, when ERG11 SNPs were included in the analysis, there is a clear correlation between low FLC accumulation and isolates that have one of five ERG11 variants and also high FLC accumulation and isolates that have non-variant ERG11 sequences. The ERG11 mutations F126L, K143R, V125/F126L, Y132F, or Y501H are correlated to fluconazole resistance and reduced fluconazole accumulation. This is a unique characteristic of C. auris, suggesting mutations in ERG11 can cause changes in the ergosterol biosynthesis pathway and membrane composition, organization, and permeability.IMPORTANCECandidozyma auris is a global human health threat because of its near-universal resistance to the antifungal fluconazole as well as a predisposition to multidrug resistance among clinical isolates. The underlying mechanisms of antifungal drug resistance in this species are still largely under investigation, and these efforts are significantly supported by research that increase our understanding of unique aspects of C. auris biology. We have identified a correlation between C. auris isolates' susceptibility to fluconazole and intracellular drug accumulation in which drug-resistant isolates have significantly reduced intracellular fluconazole compared to isolates that are susceptible to fluconazole. We have proposed a mechanism for this phenomenon and demonstrated important roles for mutations in ERG11, TAC1B, and CDR1 gene sequences for drug resistance.

Indexed as

Antifungal AgentsDrug Resistance, FungalFluconazoleFungal ProteinsMembrane Transport ProteinsMutationMicrobial Sensitivity TestsPolymorphism, Single NucleotideAntifungal AgentsFluconazoleFungal ProteinsMembrane Transport ProteinsC. aurisdrug accumulationdrug effluxdrug importfluconazolemechanisms of resistance

Identifiers

PMID41649269
PMCPMC12977551

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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.