Evidence map›Paper›PMID 15215099›Full record

ArticleAntimicrobial agents and chemotherapy2004

Extra copies of the Aspergillus fumigatus squalene epoxidase gene confer resistance to terbinafine: genetic approach to studying gene dose-dependent resistance to antifungals in A. fumigatus.

Wei Liu, Gregory S May, Michail S Lionakis, Russell E Lewis, Dimitrios P Kontoyiannis

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

18 citing papers in PubMed, 55 citations in OpenAlex.

  1. Role of Squalene Epoxidase Gene (Journal of fungi (Basel, Switzerland) · 2024
    Article
  2. Article
  3. Phylogeny, Antifungal Susceptibility, and Point Mutations ofFrontiers in cellular and infection microbiology · 2022
    Article
  4. Review
  5. F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase.Proceedings of the National Academy of Sciences of the United States of America · 2016
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  10. Review
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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

5 authors at 2 institutions in 1 country.

Wei LiuDepartment of Infectious Diseases, Infection Control and Employee Health, Unit 402, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Gregory S May
Michail S Lionakis
Russell E Lewis
Dimitrios P Kontoyiannis
University of Houston · USThe University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

With the increasing use of antifungals such as amphotericin B, itraconazole, voriconazole, caspofungin, and terbinafine (TRB) in patients at high risk for invasive aspergillosis, resistance of Aspergillus fumigatus to these agents will ultimately emerge. Due to the limited availability of molecular genetics for A. fumigatus, few studies have addressed its mechanisms of resistance to antifungals. We transformed A. fumigatus protoplasts with a pyrG-based A. fumigatus genomic DNA library (constructed in the multicopy nonintegrating vector pRG3-AMA1-NotI, which also has the pyr-4 gene for selection). We obtained one pyrG(+) transformant that grew in medium containing a fungicidal concentration (0.625 microg/ml) of TRB. To determine whether TRB resistance in that transformant was plasmid dependent, we evicted the plasmid and found concomitant loss of uracil prototrophy and TRB resistance. DNA sequence analysis identified the gene responsible for TRB resistance as the A. fumigatus squalene epoxidase gene (ERG1), which encodes the target enzyme of TRB. Authentic A. fumigatus ERG1, amplified from the genome and cloned into pRG3-AMA1-NotI, also conferred TRB-specific resistance. This molecular approach has the potential to enhance our knowledge of the mechanisms of A. fumigatus resistance to modern antifungals.

Indexed as

Amino Acid SequenceAntifungal AgentsAspergillus fumigatusCloning, MolecularCulture MediaDNA FragmentationDrug Resistance, FungalGene DosageGene LibraryMicrobial Sensitivity TestsMolecular Sequence DataNaphthalenesOxygenasesPlasmidsProtoplastsSqualene MonooxygenaseAntifungal AgentsCulture MediaNaphthalenesOxygenasesSqualene MonooxygenaseTerbinafine

Identifiers

PMID15215099
PMCPMC434218
OpenAlexW2104217343

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.