Evidence map›Paper›PMID 26643330›Full record

ArticleAntimicrobial agents and chemotherapy2015

Fluconazole Susceptibility in Cryptococcus gattii Is Dependent on the ABC Transporter Pdr11.

Mai Lee Yang, John Uhrig, Kiem Vu, Anil Singapuri, Michael Dennis, Angie Gelli, George R Thompson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 24 citations in OpenAlex.

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  8. Molecular Confirmation of the Linkage between theAntimicrobial agents and chemotherapy · 2018
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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

7 authors at 2 institutions in 1 country.

Mai Lee YangDepartment of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California-Davis, Davis, California, USA.
John UhrigDepartment of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA.
Kiem VuDepartment of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA.
Anil SingapuriDepartment of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California-Davis, Davis, California, USA.
Michael DennisDepartment of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California-Davis, Davis, California, USA.
Angie GelliDepartment of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA acgelli@ucdavis.edu grthompson@ucdavis.edu.ORCID http://orcid.org/0000-0003-3351-0683
George R ThompsonDepartment of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California-Davis, Davis, California, USA Department of Internal Medicine, Division of Infectious Diseases, University of California-Davis Medical Center, University of California-Davis, Davis, California, USA acgelli@ucdavis.edu grthompson@ucdavis.edu.
University of California, Davis · USUniversity of California Davis Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cryptococcus gattii isolates from the Pacific Northwest have exhibited higher fluconazole MICs than isolates from other sites. The mechanism of fluconazole resistance in C. gattii is unknown. We sought to determine the role of the efflux pumps Mdr1 and Pdr11 in fluconazole susceptibility. Using biolistic transformation of the parent isolate, we created a strain lacking Mdr1 (mdr1Δ) and another strain lacking Pdr11 (pdr11Δ). Phenotypic virulence factors were assessed by standard methods (capsule size, melanin production, growth at 30 and 37 °C). Survival was assessed in an intranasal murine model of cryptococcosis. Antifungal MICs were determined by the M27-A3 methodology. No differences in key virulence phenotypic components were identified. Fluconazole susceptibility was unchanged in the Mdr1 knockout or reconstituted isolates. However, fluconazole MICs decreased from 32 μg/ml for the wild-type isolate to <0.03 μg/ml for the pdr11Δ strain and reverted to 32 μg/ml for the reconstituted strain. In murine models, no difference in virulence was observed between wild-type, knockout, or reconstituted isolates. We conclude that Pdr11 plays an essential role in fluconazole susceptibility in C. gattii. Genomic and expression differences between resistant and susceptible C. gattii clinical isolates should be assessed further in order to identify other potential mechanisms of resistance.

Indexed as

AgedAnimalsAntifungal AgentsATP-Binding Cassette TransportersCryptococcosisCryptococcus gattiiDrug Resistance, FungalFemaleFluconazoleFungal ProteinsHumansMaleMice, Inbred StrainsMicrobial Sensitivity TestsAntifungal AgentsATP-Binding Cassette TransportersFluconazoleFungal ProteinsMDR1 protein, Filobasidiella neoformans

Identifiers

PMID26643330
PMCPMC4775963
OpenAlexW2276499295

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.