Evidence map›Paper›PMID 26295576›Full record

ArticlePloS one2015

The Aspergillus fumigatus pkcA G579R Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model.

Marina Campos Rocha, Krissia Franco de Godoy, Patrícia Alves de Castro, Juliana Issa Hori, Vinícius Leite Pedro Bom, Neil Andrew Brown, Anderson Ferreira da Cunha, Gustavo Henrique Goldman, Iran Malavazi

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–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

37 citing papers in PubMed.

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  8. TheJournal of fungi (Basel, Switzerland) · 2024
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  12. Survival Factor A (SvfA) Contributes toJournal of fungi (Basel, Switzerland) · 2023
    Article
  13. Chitin Biosynthesis inJournal of fungi (Basel, Switzerland) · 2023
    Review
  14. Article
  15. TheJournal of fungi (Basel, Switzerland) · 2022
    Article
  16. Review
  17. Article
  18. Article
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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

9 authors.

Marina Campos RochaDepartamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
Krissia Franco de GodoyDepartamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
Patrícia Alves de CastroDepartamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Juliana Issa HoriDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Vinícius Leite Pedro BomDepartamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Neil Andrew BrownDepartment of Plant Biology and Crop Science, Rothamsted Research, Harpenden, Herts, United Kingdom.
Anderson Ferreira da CunhaDepartamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
Gustavo Henrique GoldmanDepartamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil; Laboratório Nacional de Ciência e Tecnologia do Bioetanol, Campinas, São Paulo, Brazil.
Iran MalavaziDepartamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In A. fumigatus this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. In this study we investigated the role of protein kinase C (PkcA) in this signaling cascade. Our results suggest that pkcA is an essential gene and is activated in response to cell wall stress. Subsequently, we constructed and analyzed a non-essential A. fumigatus pkcAG579R mutant, carrying a Gly579Arg substitution in the PkcA C1B regulatory domain. The pkcAG579R mutation has a reduced activation of the downstream Mitogen-Activated Protein Kinase, MpkA, resulting in the altered expression of genes encoding cell wall-related proteins, markers of endoplasmic reticulum stress and the unfolded protein response. Furthermore, PkcAG579R is involved in the formation of proper conidial architecture and protection to oxidative damage. The pkcAG579R mutant elicits increased production of TNF-α and phagocytosis but it has no impact on virulence in a murine model of invasive pulmonary aspergillosis. These results highlight the importance of PkcA to the CWI pathway but also indicated that additional regulatory circuits may be involved in the biosynthesis and/or reinforcement of the A. fumigatus cell wall during infection.

Indexed as

Gene Expression Regulation, FungalAnimalsAspergillus fumigatusCell WallDisease Models, AnimalEndoplasmic Reticulum StressFemaleFungal ProteinsGenetic EngineeringHumansInvasive Pulmonary AspergillosisMiceMice, Inbred BALB CMitogen-Activated Protein KinasesMutationNeutropeniaFungal ProteinsMitogen-Activated Protein KinasesProtein Kinase C-alphaTumor Necrosis Factor-alpha

Identifiers

PMID26295576
PMCPMC4546635

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Registered trials

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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.