Evidence map›Paper›PMID 35303047›Full record

ArticlePloS one2022

CRISPR-Cas9 approach confirms Calcineurin-responsive zinc finger 1 (Crz1) transcription factor as a promising therapeutic target in echinocandin-resistant Candida glabrata.

Andres Ceballos-Garzon, Elvira Roman, Jesús Pla, Fabrice Pagniez, Daniela Amado, Carlos J Alméciga-Díaz, Patrice Le Pape, Claudia M Parra-Giraldo

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-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

8 citing papers in PubMed, 14 citations in OpenAlex.

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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

8 authors at 3 institutions in 3 countries.

Andres Ceballos-GarzonUnidad de Proteómica y Micosis Humanas, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.ORCID 0000-0002-0743-6857
Elvira RomanDepartamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad Complutense de Madrid, Madrid, Spain.
Jesús PlaDepartamento de Microbiología y Parasitología, Facultad de Farmacia, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Universidad Complutense de Madrid, Madrid, Spain.
Fabrice PagniezDepartment of Parasitology and Medical Mycology, Faculty of Pharmacy, University of Nantes, Nantes, France.ORCID 0000-0002-1759-5106
Daniela AmadoUnidad de Proteómica y Micosis Humanas, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.ORCID 0000-0001-5796-5979
Carlos J Alméciga-DíazInstitute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.ORCID 0000-0001-6484-1173
Patrice Le PapeDepartment of Parasitology and Medical Mycology, Faculty of Pharmacy, University of Nantes, Nantes, France.ORCID 0000-0001-5059-6402
Claudia M Parra-GiraldoUnidad de Proteómica y Micosis Humanas, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.ORCID 0000-0003-1302-5429
Pontificia Universidad Javeriana · CONantes Université · FRUniversidad Complutense de Madrid · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Invasive fungal infections, which kill more than 1.6 million patients each year worldwide, are difficult to treat due to the limited number of antifungal drugs (azoles, echinocandins, and polyenes) and the emergence of antifungal resistance. The transcription factor Crz1, a key regulator of cellular stress responses and virulence, is an attractive therapeutic target because this protein is absent in human cells. Here, we used a CRISPR-Cas9 approach to generate isogenic crz1Δ strains in two clinical isolates of caspofungin-resistant C. glabrata to analyze the role of this transcription factor in susceptibility to echinocandins, stress tolerance, biofilm formation, and pathogenicity in both non-vertebrate (Galleria mellonella) and vertebrate (mice) models of candidiasis. In these clinical isolates, CRZ1 disruption restores the susceptibility to echinocandins in both in vitro and in vivo models, and affects their oxidative stress response, biofilm formation, cell size, and pathogenicity. These results strongly suggest that Crz1 inhibitors may play an important role in the development of novel therapeutic agents against fungal infections considering the emergence of antifungal resistance and the low number of available antifungal drugs.

Indexed as

Candida glabrataEchinocandinsAnimalsAntifungal AgentsCalcineurinCRISPR-Cas SystemsDrug Resistance, FungalHumansMiceMicrobial Sensitivity TestsTranscription FactorsZincZinc FingersAntifungal AgentsCalcineurinEchinocandinsTranscription FactorsZinc

Identifiers

PMID35303047
PMCPMC8932611
OpenAlexW4220834332

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.