Evidence map›Paper›PMID 34915074›Full record

ArticleClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2022

In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris.

Jeffrey M Rybak, Katherine S Barker, José F Muñoz, Josie E Parker, Suhail Ahmad, Eiman Mokaddas, Aneesa Abdullah, Rehab S Elhagracy, Steve L Kelly, Christina A Cuomo and 1 more

Open access · greenAbstract read
In one paragraph

Article in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% of its field
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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Beyond intrinsic resistance: novel insights into the emergence and management of resistance acquired in Candida auris upon antifungal exposure.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Review
  6. Article
  7. Review
  8. Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026
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  10. Microbiology and molecular biology reviews : MMBR · 2026
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  12. Comprehensive Insights into Sugar Transporters ofJournal of fungi (Basel, Switzerland) · 2026
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  13. Article
  14. bioRxiv : the preprint server for biology · 2026
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  15. Resistance gene mutations and phylogenetic relationships inFrontiers in cellular and infection microbiology · 2026
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  16. Article
  17. Article
  18. Genomic epidemiology of Colombian resistantAntimicrobial agents and chemotherapy · 2025
    Article
  19. Acquired amphotericin B resistance attributed to a mutatedAntimicrobial agents and chemotherapy · 2025
    Article
  20. mSphere · 2025
    Article

25 more citing papers are in PubMed but not listed here.

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

11 authors at 6 institutions in 3 countries.

Jeffrey M RybakDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: jrybak@stjude.org.
Katherine S BarkerDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
José F MuñozBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Josie E ParkerCentre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, UK.
Suhail AhmadDepartment of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
Eiman MokaddasDepartment of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait; Department of Microbiology, Ibn Sina Hospital, Shuwaikh, Kuwait.
Aneesa AbdullahDepartment of Microbiology, Ibn Sina Hospital, Shuwaikh, Kuwait.
Rehab S ElhagracyDepartment of Haematology, Kuwait Cancer Control Center, Shuwaikh, Kuwait.
Steve L KellyCentre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, UK.
Christina A CuomoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
P David RogersDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: dave.rogers@stjude.org.
St. Jude Children's Research Hospital · USBroad Institute · USKuwait University · KWSwansea University · GBIbn Sina Hospital · KWKuwait Cancer Control Center · KW

Funding

Novel Azole Resistance Mechanisms in Candida albicansR01AI058145 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROGERS, P. DAVID · 2005 to 2021
$5.8M
NIAID NIH HHS R01 AI058145
6 · The paper itself

Abstract

objectiveCandida auris has emerged as a health-care-associated and multidrug-resistant fungal pathogen of great clinical concern. As many as 50% of C. auris clinical isolates are reported to be resistant to amphotericin B, but no mechanisms contributing to this resistance have been identified. Here we describe a clinical case in which high-level amphotericin B resistance was acquired in vivo during therapy and undertake molecular and genetic studies to identify and characterize the genetic determinant of resistance.

methodsWhole-genome sequencing was performed on four C. auris isolates obtained from a single patient case. Cas9-mediated genetic manipulations were then used to generate mutant strains harbouring mutations of interest, and these strains were subsequently subjected to amphotericin B susceptibility testing and comprehensive sterol profiling.

resultsA novel mutation in the C. auris sterol-methyltransferase gene ERG6 was found to be associated with amphotericin B resistance, and this mutation alone conferred a >32-fold increase in amphotericin B resistance. Comprehensive sterol profiling revealed an abrogation of ergosterol biosynthesis and a corresponding accumulation of cholesta-type sterols in isolates and strains harbouring the clinically derived ERG6 mutation.

conclusionsTogether these findings definitively demonstrate mutations in C. auris ERG6 as the first identified mechanism of clinical amphotericin B resistance in C. auris and represent a significant step forward in the understanding of antifungal resistance in this emerging public health threat.

Indexed as

Amphotericin BCandida aurisAntifungal AgentsHumansMicrobial Sensitivity TestsSterolsAmphotericin BAntifungal AgentsSterolsAmphotericin BCandida aurisERG6In vivo evolutionResistance

Identifiers

PMID34915074
PMCPMC9467277
OpenAlexW4213354765

What OpenQuestion holds

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Registered trials

None linked

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.