Evidence map›Paper›PMID 17371828›Full record

ArticleAntimicrobial agents and chemotherapy2007

A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations.

E Mellado, G Garcia-Effron, L Alcázar-Fuoli, W J G Melchers, P E Verweij, M Cuenca-Estrella, J L Rodríguez-Tudela

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
230citing papers in PubMed, 1 pooled it
–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

230 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016
    Guideline
  2. Article
  3. Article
  4. Article
  5. Genotype-Phenotype Relationships in Azole-ResistantJournal of fungi (Basel, Switzerland) · 2026
    Review
  6. Global epidemiology of azole resistance inJAC-antimicrobial resistance · 2026
    Review
  7. Review
  8. Pathogenesis and Triazole Resistance inInfection and drug resistance · 2026
    Review
  9. Understanding multi-azole resistance inFrontiers in fungal biology · 2026
    Article
  10. Review
  11. Article
  12. Azole-ResistantJournal of fungi (Basel, Switzerland) · 2025
    Review
  13. Article
  14. Whole-chromosome duplications drive antimicrobial resistance inbioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Formulation, characterization, andCurrent medical mycology · 2025
    Article
  20. Review

170 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

7 authors.

E MelladoServicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain. emellado@isciii.es
G Garcia-Effron
L Alcázar-Fuoli
W J G Melchers
P E Verweij
M Cuenca-Estrella
J L Rodríguez-Tudela

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fourteen Aspergillus fumigatus clinical isolates that exhibited a pattern of reduced susceptibility to triazole drugs were analyzed. The sequences of the cyp51A gene from all isolates showed the presence of a point mutation at t364a, which led to the substitution of leucine 98 for histidine (L98H), together with the presence of two copies of a 34-bp sequence in tandem in the promoter of the cyp51A gene. Quantitative expression analysis (real-time PCR) showed up to an eightfold increase in the level of expression of the cyp51A gene compared to that by the susceptible strain. Three PCR fragments of one azole-resistant strain (strain CM2627) that included the promoter with the tandem repeat and part of cyp51A with the t364a mutation or PCR fragments with only one of the modifications were used to replace the cyp51A gene of an azole drug-susceptible A. fumigatus wild-type strain (strain CM237). Only transformants which had incorporated the tandem repeat in the promoter of the cyp51A gene and the L98H amino acid substitution exhibited similarly reduced patterns of susceptibility to all triazole agents and similarly increased levels of cyp51A expression, confirming that the combination of both alterations was responsible for the azole-resistant phenotype.

Indexed as

Amino Acid SubstitutionAntifungal AgentsAspergillus fumigatusAzolesCytochrome P-450 Enzyme SystemDrug Resistance, FungalFungal ProteinsGenotypeHumansMicrobial Sensitivity TestsTandem Repeat SequencesAntifungal AgentsAzolescytochrome P-450 CYP51A, AspergillusCytochrome P-450 Enzyme SystemFungal Proteins

Identifiers

PMID17371828
PMCPMC1891382

What OpenQuestion holds

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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.