State-of-Art in Aspergillus

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Plant, Algae and Fungi Cell Biology".

Deadline for manuscript submissions: closed (25 February 2023) | Viewed by 12807

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Engineering, Woosuk University,443 Samrye-ro, Wanju, Jeonbuk 55338, Korea
Interests: filamentous fungi; Aspergillus; molecular genetics and genomics; development; signal transduction; secondary metabolism
Special Issues, Collections and Topics in MDPI journals
School of Food Science and Biotechnology , Kyungpook National University, 80, Daehak-ro, Buk-gu, Daegu 41566, Korea
Interests: Aspergillus species; fungal development; sporogenesis; fungal metabolites; heterologous gene expression; fungal genetics

Special Issue Information

Dear Colleagues,

Aspergilli are ubiquitous filamentous fungi that have beneficial and/or detrimental effects on humankind and the environment. Some Aspergillus species, such as Aspergillus fumigatus, can seriously affect public health by causing invasive aspergillosis or allergic bronchopulmonary aspergillosis. Several species, including Aspergillus flavus and Aspergillus parasiticus, can contaminate plant-based foods and feeds with mycotoxin aflatoxins, which are the most potent carcinogens found in nature. The consumption of aflatoxin-contaminated foods or feeds can result in severe illness, including aflatoxicosis, liver necrosis, and/or liver cancer. On the other hand, many Aspergillus species are used for enzyme production, food fermentations, biotechnology, and the production of pharmaceuticals. For example, Aspergillus oryzae is widely used for traditional food fermentations in East Asia. Aspergillus niger is used to produce various enzymes and organic acids. Therefore, it is very important to elucidate the molecular and cellular mechanisms for understanding the life of various Aspergillus species.

The aim of this Special Issue is to provide current research regarding various aspects of the molecular and cellular mechanisms of Aspergillus in order to share valuable information beneficial to the fungal research community.

As a Guest Editor of the Special Issue, I invite you to submit research articles, review articles, and short communications related to Aspergillus molecular biology, signal transduction, genetics and genomics, and secondary metabolism.

Prof. Kap-Hoon Han
Dr. Hee-Soo Park
Guest Editors

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Keywords

  • Aspergillus
  • genetics and genomics
  • molecular mechanism
  • secondary metabolism
  • signal transduction

Published Papers (5 papers)

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Research

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16 pages, 1804 KiB  
Article
Genome-Wide Gene Expression Analyses of the AtfA/AtfB-Mediated Menadione Stress Response in Aspergillus nidulans
by Beatrix Kocsis, Mi-Kyung Lee, Károly Antal, Jae-Hyuk Yu, István Pócsi, Éva Leiter and Tamás Emri
Cells 2023, 12(3), 463; https://doi.org/10.3390/cells12030463 - 31 Jan 2023
Cited by 3 | Viewed by 1479
Abstract
The bZIP transcription factors (TFs) govern regulation of development, secondary metabolism, and various stress responses in filamentous fungi. In this work, we carried out genome-wide expression studies employing Illumina RNAseq to understand the roles of the two bZIP transcription factors AtfA and AtfB [...] Read more.
The bZIP transcription factors (TFs) govern regulation of development, secondary metabolism, and various stress responses in filamentous fungi. In this work, we carried out genome-wide expression studies employing Illumina RNAseq to understand the roles of the two bZIP transcription factors AtfA and AtfB in Aspergillus nidulans. Comparative analyses of transcriptomes of control, ΔatfA, ΔatfB, and ΔatfAΔatfB mutant strains were performed. Dependence of a gene on AtfA (AtfB) was decided by its differential downregulation both between the reference and ΔatfAatfB) strains and between the ΔatfBatfA) and the ΔatfAΔatfB strains in vegetatively grown cells (mycelia) and asexual spores (conidia) of menadione sodium bisulfite (MSB)-treated or untreated cultures. As AtfA is the primary bZIP TF governing stress-response in A. nidulans, the number of differentially expressed genes for ΔatfA was significantly higher than for ΔatfB in both mycelial and conidial samples, and most of the AtfB-dependent genes showed AtfA dependence, too. Moreover, the low number of genes depending on AtfB but not on AtfA can be a consequence of ΔatfA leading to downregulation of atfB expression. Conidial samples showed much higher abundance of atfA and atfB mRNAs and more AtfA- and AtfB-affected genes than mycelial samples. In the presence of MSB, the number of AtfB- (but not of AtfA-) affected genes decreased markedly, which was accompanied with decreased mRNA levels of atfB in MSB-treated mycelial (reference strain) and conidial (ΔatfA mutant) samples. In mycelia, the overlap between the AtfA-dependent genes in MSB-treated and in untreated samples was low, demonstrating that distinct genes can be under AtfA control under different conditions. Carbohydrate metabolism genes were enriched in the set of AtfA-dependent genes. Among them, AtfA-dependence of glycolytic genes in conidial samples was the most notable. Levels of transcripts of certain secondary metabolitic gene clusters, such as the Emericellamide cluster, also showed AtfA-dependent regulation. Genes encoding catalase and histidine-containing phosphotransfer proteins showed AtfA-dependence under all experimental conditions. There were 23 AtfB-dependent genes that did not depend on AtfA under any of our experimental conditions. These included a putative α-glucosidase (agdB), a putative α-amylase, calA, which is involved in early conidial germination, and an alternative oxidase. In summary, in A. nidulans there is a complex interaction between the two bZIP transcription factors, where AtfA plays the primary regulatory role. Full article
(This article belongs to the Special Issue State-of-Art in Aspergillus)
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15 pages, 4886 KiB  
Article
The Putative C2H2 Transcription Factor VadH Governs Development, Osmotic Stress Response, and Sterigmatocystin Production in Aspergillus nidulans
by Xiaoyu Li, Yanxia Zhao, Heungyun Moon, Jieyin Lim, Hee-Soo Park, Zhiqiang Liu and Jae-Hyuk Yu
Cells 2022, 11(24), 3998; https://doi.org/10.3390/cells11243998 - 10 Dec 2022
Cited by 1 | Viewed by 1692
Abstract
The VosA-VelB hetero-dimeric complex plays a pivotal role in regulating development and secondary metabolism in Aspergillus nidulans. In this work, we characterize a new VosA/VelB-activated gene called vadH, which is predicted to encode a 457-amino acid length protein containing four adjacent [...] Read more.
The VosA-VelB hetero-dimeric complex plays a pivotal role in regulating development and secondary metabolism in Aspergillus nidulans. In this work, we characterize a new VosA/VelB-activated gene called vadH, which is predicted to encode a 457-amino acid length protein containing four adjacent C2H2 zinc-finger domains. Mutational inactivation of vosA or velB led to reduced mRNA levels of vadH throughout the lifecycle, suggesting that VosA and VelB have a positive regulatory effect on the expression of vadH. The deletion of vadH resulted in decreased asexual development (conidiation) but elevated production of sexual fruiting bodies (cleistothecia), indicating that VadH balances asexual and sexual development in A. nidulans. Moreover, the vadH deletion mutant exhibited elevated susceptibility to hyperosmotic stress compared to wild type and showed elevated production of the mycotoxin sterigmatocystin (ST). Genome-wide expression analyses employing RNA-Seq have revealed that VadH is likely involved in regulating more genes and biological pathways in the developmental stages than those in the vegetative growth stage. The brlA, abaA, and wetA genes of the central regulatory pathway for conidiation are downregulated significantly in the vadH null mutant during asexual development. VadH also participates in regulating the genes, mat2, ppgA and lsdA, etc., related to sexual development, and some of the genes in the ST biosynthetic gene cluster. In summary, VadH is a putative transcription factor with four C2H2 finger domains and is involved in regulating asexual/sexual development, osmotic stress response, and ST production in A. nidulans. Full article
(This article belongs to the Special Issue State-of-Art in Aspergillus)
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13 pages, 2812 KiB  
Article
BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
by Vincenzo Nasillo, Ivana Lagreca, Daniela Vallerini, Patrizia Barozzi, Giovanni Riva, Monica Maccaferri, Ambra Paolini, Fabio Forghieri, Stefania Fiorcari, Rossana Maffei, Silvia Martinelli, Claudio Giacinto Atene, Ilaria Castelli, Roberto Marasca, Leonardo Potenza, Patrizia Comoli, Rossella Manfredini, Enrico Tagliafico, Tommaso Trenti and Mario Luppi
Cells 2022, 11(6), 1003; https://doi.org/10.3390/cells11061003 - 16 Mar 2022
Cited by 7 | Viewed by 2768
Abstract
In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an [...] Read more.
In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients. Full article
(This article belongs to the Special Issue State-of-Art in Aspergillus)
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Review

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19 pages, 2960 KiB  
Review
Upstream Regulation of Development and Secondary Metabolism in Aspergillus Species
by Heungyun Moon, Kap-Hoon Han and Jae-Hyuk Yu
Cells 2023, 12(1), 2; https://doi.org/10.3390/cells12010002 - 20 Dec 2022
Cited by 7 | Viewed by 2103
Abstract
In filamentous fungal Aspergillus species, growth, development, and secondary metabolism are genetically programmed biological processes, which require precise coordination of diverse signaling elements, transcription factors (TFs), upstream and downstream regulators, and biosynthetic genes. For the last few decades, regulatory roles of these controllers [...] Read more.
In filamentous fungal Aspergillus species, growth, development, and secondary metabolism are genetically programmed biological processes, which require precise coordination of diverse signaling elements, transcription factors (TFs), upstream and downstream regulators, and biosynthetic genes. For the last few decades, regulatory roles of these controllers in asexual/sexual development and primary/secondary metabolism of Aspergillus species have been extensively studied. Among a wide spectrum of regulators, a handful of global regulators govern upstream regulation of development and metabolism by directly and/or indirectly affecting the expression of various genes including TFs. In this review, with the model fungus Aspergillus nidulans as the central figure, we summarize the most well-studied main upstream regulators and their regulatory roles. Specifically, we present key functions of heterotrimeric G proteins and G protein-coupled receptors in signal transduction), the velvet family proteins governing development and metabolism, LaeA as a global regulator of secondary metabolism, and NsdD, a key GATA-type TF, affecting development and secondary metabolism and provide a snapshot of overall upstream regulatory processes underlying growth, development, and metabolism in Aspergillus fungi. Full article
(This article belongs to the Special Issue State-of-Art in Aspergillus)
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17 pages, 2992 KiB  
Review
Regulation of Conidiogenesis in Aspergillus flavus
by He-Jin Cho, Sung-Hun Son, Wanping Chen, Ye-Eun Son, Inhyung Lee, Jae-Hyuk Yu and Hee-Soo Park
Cells 2022, 11(18), 2796; https://doi.org/10.3390/cells11182796 - 07 Sep 2022
Cited by 27 | Viewed by 3845
Abstract
Aspergillus flavus is a representative fungal species in the Aspergillus section Flavi and has been used as a model system to gain insights into fungal development and toxin production. A. flavus has several adverse effects on humans, including the production of the most [...] Read more.
Aspergillus flavus is a representative fungal species in the Aspergillus section Flavi and has been used as a model system to gain insights into fungal development and toxin production. A. flavus has several adverse effects on humans, including the production of the most carcinogenic mycotoxin aflatoxins and causing aspergillosis in immune-compromised patients. In addition, A. flavus infection of crops results in economic losses due to yield loss and aflatoxin contamination. A. flavus is a saprophytic fungus that disperses in the ecosystem mainly by producing asexual spores (conidia), which also provide long-term survival in the harsh environmental conditions. Conidia are composed of the rodlet layer, cell wall, and melanin and are produced from an asexual specialized structure called the conidiophore. The production of conidiophores is tightly regulated by various regulators, including the central regulatory cascade composed of BrlA-AbaA-WetA, the fungi-specific velvet regulators, upstream regulators, and developmental repressors. In this review, we summarize the findings of a series of recent studies related to asexual development in A. flavus and provide insights for a better understanding of other fungal species in the section Flavi. Full article
(This article belongs to the Special Issue State-of-Art in Aspergillus)
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