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Novel biological functions of the nsdc transcription factor in aspergillus fumigatus
de Castro, Patrícia Alves1; Valero, Clara1; Chiaratto, Jéssica1; Colabardini, Ana Cristina1,2; Pardeshi, Lakhansing2,3; Silva, Lilian Pereira1; Almeida, Fausto4; Rocha, Marina Campos5; Silva, Roberto Nascimento4; Malavazi, Iran5; Du, Wenyue6; Dyer, Paul S.6; Brock, Matthias6; Loures, Flávio Vieira7; Wong, Koon Ho2,8; Goldman, Gustavo H.1
2021-01-05
Source PublicationmBio
ISSN2150-7511
Volume12Pages:1-25
Abstract

The fungal zinc finger transcription factor NsdC is named after, and is best known for, its essential role in sexual reproduction (never in sexual develop-ment). 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 devel-opment, 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. IMPORTANCE Aspergillus 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 path-ways. 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.

KeywordAspergillus Fumigatus Calcium Signaling Cell Wall Integrity Pathway Sexual Cycle Transcription Factor Transcription Factors
DOI10.1128/mBio.03102-20
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaMicrobiology
WOS SubjectMicrobiology
WOS IDWOS:000608245600013
PublisherAMER SOC MICROBIOLOGY1752 N ST NW, WASHINGTON, DC 20036-2904
Scopus ID2-s2.0-85099190294
Fulltext Access
Citation statistics
Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Translational Medicine
Genomics, Bioinformatics and Single Cell Analysis Core
Corresponding AuthorGoldman, Gustavo H.
Affiliation1.Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
2.Faculty of Health Sciences, University of Macau, Taipa, China
3.Genomics and Bioinformatics Core, Faculty of Health Sciences, University of Macau, Taipa, China
4.Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
5.Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, Brazil
6.Fungal Genetics and Biology Group, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
7.Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, Brazil
8.Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, China
Recommended Citation
GB/T 7714
de Castro, Patrícia Alves,Valero, Clara,Chiaratto, Jéssica,et al. Novel biological functions of the nsdc transcription factor in aspergillus fumigatus[J]. mBio, 2021, 12, 1-25.
APA de Castro, Patrícia Alves., Valero, Clara., Chiaratto, Jéssica., Colabardini, Ana Cristina., Pardeshi, Lakhansing., Silva, Lilian Pereira., Almeida, Fausto., Rocha, Marina Campos., Silva, Roberto Nascimento., Malavazi, Iran., Du, Wenyue., Dyer, Paul S.., Brock, Matthias., Loures, Flávio Vieira., Wong, Koon Ho., & Goldman, Gustavo H. (2021). Novel biological functions of the nsdc transcription factor in aspergillus fumigatus. mBio, 12, 1-25.
MLA de Castro, Patrícia Alves,et al."Novel biological functions of the nsdc transcription factor in aspergillus fumigatus".mBio 12(2021):1-25.
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