Novel biological functions of the NsdC transcription factor in Aspergillus fumigatus
| Autor: | Matthias Brock, Koon Ho Wong, Wenyue Du, Paul S. Dyer, Fausto Almeida, Clara Valero, Gustavo H. Goldman, Marina Campos Rocha, Jéssica Chiaratto, Flávio V. Loures, Lakhansing Pardeshi, Patrícia Alves de Castro, Lilian Pereira Silva, Roberto Nascimento Silva, Iran Malavazi, Ana Cristina Colabardini |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Molecular Biology and Physiology Virulence Factors Genes Fungal Conidiation RNA polymerase II calcium signaling Microbiology sexual cycle Fungal Proteins Mice Cell Wall Aspergillus nidulans transcription factors Gene Expression Regulation Fungal Virology Reproduction Asexual Animals Aspergillosis skin and connective tissue diseases Gene Transcription factor transcription factor cell wall integrity pathway Zinc finger transcription factor Genetics Mice Inbred BALB C Virulence biology Aspergillus fumigatus bacterial infections and mycoses biology.organism_classification QR1-502 Sexual reproduction Mice Inbred C57BL Disease Models Animal Phenotype Cell wall organization Mutation biology.protein Female VIRULÊNCIA Transcriptome Research Article Signal Transduction |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP mBio mBio, Vol 12, Iss 1 (2021) |
| Popis: | The fungal zinc finger transcription factor NsdC is named after, and is best known for, its essential role in sexual reproduction (never in sexual development). In previous studies with Aspergillus nidulans, it was also shown to have roles in promotion of vegetative growth and suppression of asexual conidiation. In this study, the function of the nsdC homologue in the opportunistic human pathogen A. fumigatus was investigated. NsdC was again found to be essential for sexual development, with deletion of the nsdC gene in both MAT1-1 and MAT1-2 mating partners of a cross leading to complete loss of fertility. However, a functional copy of nsdC in one mating partner was sufficient to allow sexual reproduction. Deletion of nsdC also led to decreased vegetative growth and allowed conidiation in liquid cultures, again consistent with previous findings. However, NsdC in A. fumigatus was shown to have additional biological functions including response to calcium stress, correct organization of cell wall structure, and response to the cell wall stressors. Furthermore, virulence and host immune recognition were affected. Gene expression studies involving chromatin immunoprecipitation (ChIP) of RNA polymerase II (PolII) coupled to next-generation sequencing (Seq) revealed that deletion of nsdC resulted in changes in expression of over 620 genes under basal growth conditions. This demonstrated that this transcription factor mediates the activity of a wide variety of signaling and metabolic pathways and indicates that despite the naming of the gene, the promotion of sexual reproduction is just one among multiple roles of NsdC. IMPORTANCEAspergillus fumigatus is an opportunistic human fungal pathogen and the main causal agent of invasive aspergillosis, a life-threatening infection especially in immunocompromised patients. A. fumigatus can undergo both asexual and sexual reproductive cycles, and the regulation of both cycles involves several genes and pathways. Here, we have characterized one of these genetic determinants, the NsdC transcription factor, which was initially identified in a screen of transcription factor null mutants showing sensitivity when exposed to high concentrations of calcium. In addition to its known essential roles in sexual reproduction and control of growth rate and asexual reproduction, we have shown in the present study that A. fumigatus NsdC transcription factor has additional previously unrecognized biological functions including calcium tolerance, cell wall stress response, and correct cell wall organization and functions in virulence and host immune recognition. Our results indicate that NsdC can play novel additional biological functions not directly related to its role played during sexual and asexual processes. |
| Databáze: | OpenAIRE |
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