Evidence map›Paper›PMID 35041649›Full record

ArticlePLoS genetics2022

Regulation of gliotoxin biosynthesis and protection in Aspergillus species.

Patrícia Alves de Castro, Ana Cristina Colabardini, Maísa Moraes, Maria Augusta Crivelente Horta, Sonja L Knowles, Huzefa A Raja, Nicholas H Oberlies, Yasuji Koyama, Masahiro Ogawa, Katsuya Gomi and 7 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

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  17. The Transcriptome Response to Azole Compounds inJournal of fungi (Basel, Switzerland) · 2023
    Article
  18. Article
  19. Review
  20. Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022
    Review
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

17 authors at 7 institutions in 5 countries.

Patrícia Alves de CastroFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.ORCID 0000-0003-3045-6511
Ana Cristina ColabardiniFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Maísa MoraesFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.ORCID 0000-0001-8977-9329
Maria Augusta Crivelente HortaFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.ORCID 0000-0003-2159-5296
Sonja L KnowlesDepartment of Chemistry and Biochemistry, University of North Carolina at Greensboro, North Carolina United States of America.ORCID 0000-0002-6295-231X
Huzefa A RajaDepartment of Chemistry and Biochemistry, University of North Carolina at Greensboro, North Carolina United States of America.ORCID 0000-0002-0824-9463
Nicholas H OberliesDepartment of Chemistry and Biochemistry, University of North Carolina at Greensboro, North Carolina United States of America.ORCID 0000-0002-0354-8464
Yasuji KoyamaNoda Institute for Scientific Research, 338 Noda, Chiba, Japan.ORCID 0000-0002-4754-3307
Masahiro OgawaNoda Institute for Scientific Research, 338 Noda, Chiba, Japan.
Katsuya GomiDepartment of Bioindustrial Informatics and Genomics, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.ORCID 0000-0003-3463-8072
Jacob L SteenwykDepartment of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.ORCID 0000-0002-8436-595X
Antonis RokasDepartment of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
Relber A GonçalesLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.ORCID 0000-0002-3037-3663
Cláudio Duarte-OliveiraLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.ORCID 0000-0002-8540-0753
Agostinho CarvalhoLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.ORCID 0000-0001-8935-8030
Laure N A RiesMRC Centre for Medical Mycology at the University of Exeter, Geoffrey Pope Building, Exeter, United Kingdom.ORCID 0000-0001-9653-3159
Gustavo H GoldmanFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.ORCID 0000-0002-2986-350X
Universidade de São Paulo · BRUniversity of Minho · PTUniversity of North Carolina at Greensboro · USNoda Institute for Scientific Research · JPVanderbilt University · USTohoku University · JPUniversity of Exeter · GB

Funding

Deciphering the phenotypic and genomic traits that underlie the evolution of pathogenicity differences among Aspergillus fumigatus and its close relativesR01AI153356 · NIAID · VANDERBILT UNIVERSITY · PI Antonis Rokas · 2022 to 2026
$3.5M
Deciphering the phenotypic and genomic traits that underlie the evolution of pathogenicity differences among Aspergillus fumigatus and its close relativesR56AI146096 · NIAID · VANDERBILT UNIVERSITY · PI ROKAS, ANTONIS · 2020 to 2020
$592k
Co-culturing to Elicit Chemical Diversity in FungiF31AT010558 · NCCIH · UNIVERSITY OF NORTH CAROLINA GREENSBORO · PI KNOWLES, SONJA LEE · 2019 to 2020
$65k
Howard Hughes Medical InstituteNCCIH NIH HHS F31 AT010558NIAID NIH HHS R01 AI153356NIAID NIH HHS R56 AI146096
6 · The paper itself

Abstract

Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied A. fumigatus mycotoxin with a wide range of known toxic effects that impair human immune cell function. GT is also highly toxic to A. fumigatus and this fungus has evolved self-protection mechanisms that include (i) the GT efflux pump GliA, (ii) the GT neutralising enzyme GliT, and (iii) the negative regulation of GT biosynthesis by the bis-thiomethyltransferase GtmA. The transcription factor (TF) RglT is the main regulator of GliT and this GT protection mechanism also occurs in the non-GT producing fungus A. nidulans. However, the A. nidulans genome does not encode GtmA and GliA. This work aimed at analysing the transcriptional response to exogenous GT in A. fumigatus and A. nidulans, two distantly related Aspergillus species, and to identify additional components required for GT protection. RNA-sequencing shows a highly different transcriptional response to exogenous GT with the RglT-dependent regulon also significantly differing between A. fumigatus and A. nidulans. However, we were able to observe homologs whose expression pattern was similar in both species (43 RglT-independent and 11 RglT-dependent). Based on this approach, we identified a novel RglT-dependent methyltranferase, MtrA, involved in GT protection. Taking into consideration the occurrence of RglT-independent modulated genes, we screened an A. fumigatus deletion library of 484 transcription factors (TFs) for sensitivity to GT and identified 15 TFs important for GT self-protection. Of these, the TF KojR, which is essential for kojic acid biosynthesis in Aspergillus oryzae, was also essential for virulence and GT biosynthesis in A. fumigatus, and for GT protection in A. fumigatus, A. nidulans, and A. oryzae. KojR regulates rglT, gliT, gliJ expression and sulfur metabolism in Aspergillus species. Together, this study identified conserved components required for GT protection in Aspergillus species.

Indexed as

AspergillusAspergillus fumigatusAspergillus nidulansAspergillus oryzaeFungal ProteinsGene Expression ProfilingGene Expression Regulation, FungalGliotoxinMethyltransferasesRNA-SeqTranscription FactorsFungal ProteinsGliotoxinMethyltransferasesTranscription Factors

Identifiers

PMID35041649
PMCPMC8797188
OpenAlexW4225635663

What Socratic 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 Socratic graph.