Mycotoxins and Its Gene Regulation

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 13555

Special Issue Editors

Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan
Interests: mycotoxins; gene regulation; fungal genome; Pathogenic fungi; stress responses; mathematical modelling
Dr. Daisuke Hagiwara
E-Mail Website
Guest Editor
University of Tsukuba, Faculty of Life and Environmental Sciences

Special Issue Information

Dear Collegaues,

Fungi, especially filamentous fungi, produce a diverse array of secondary metabolites (SMs), including toxic SMs, also known as mycotoxins. While among approximately 400 mycotoxins reported, most mycotoxins are known as food contamination, such as aflatoxin and ochratoxin A (OTA), some mycotoxins such as gliotoxin are involved in fungal infection in humans. Investigating the regulation mechanisms of mycotoxins is a prerequisite for controlling food contamination and pathogenicity. Comparative genomics and transcriptomics are addressing the sequence and regulation diversities of SM gene clusters, although it is conceivable that the gene regulation of SM gene clusters could be very complicated. In this Special Issue, not only current knowledge about mycotoxins but also genomics approaches with the aid of NGS are summarized.

Dr. Hiroki Takahashi
Dr. Daisuke Hagiwara
Guest Editors

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Keywords

  • mycotoxins
  • gene regulation
  • food control
  • gene cluster
  • filamentous fungi

Published Papers (5 papers)

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Research

12 pages, 2621 KiB  
Article
Time Course of Renal Transcriptomics after Subchronic Exposure to Ochratoxin A in Fisher Rats
Toxins 2021, 13(3), 177; https://doi.org/10.3390/toxins13030177 - 26 Feb 2021
Cited by 2 | Viewed by 1583
Abstract
The mycotoxin ochratoxin A (OTA) is a potent nephrocarcinogen, mainly in male rats. The aim of this study was to determine the time course of gene expression (GeneChip® Rat Gene 2.0 ST Array, Affymetrix) in kidney samples from male and female F344 [...] Read more.
The mycotoxin ochratoxin A (OTA) is a potent nephrocarcinogen, mainly in male rats. The aim of this study was to determine the time course of gene expression (GeneChip® Rat Gene 2.0 ST Array, Affymetrix) in kidney samples from male and female F344 rats, treated daily (p.o) with 0.50 mg/kg b.w. (body weight) of OTA for 7 or 21 days, and evaluate if there were differences between both sexes. After OTA treatment, there was an evolution of gene expression in the kidney over time, with more differentially expressed genes (DEG) at 21 days. The gene expression time course was different between sexes with respect to the number of DEG and the direction of expression (up or down): the female response was progressive and consistent over time, whereas males had a different early response with more DEG, most of them up-regulated. The statistically most significant DEG corresponded to metabolism enzymes (Akr1b7, Akr1c2, Adh6 down-regulated in females; Cyp2c11, Dhrs7, Cyp2d1, Cyp2d5 down-regulated in males) or transporters (Slc17a9 down-regulated in females; Slco1a1 (OATP-1) and Slc51b and Slc22a22 (OAT) down-regulated in males). Some of these genes had also a basal sex difference and were over-expressed in males or females with respect to the other sex. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
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14 pages, 3698 KiB  
Article
Functional Role of Aspergillus carbonarius AcOTAbZIP Gene, a bZIP Transcription Factor within the OTA Gene Cluster
Toxins 2021, 13(2), 111; https://doi.org/10.3390/toxins13020111 - 02 Feb 2021
Cited by 14 | Viewed by 2647
Abstract
Aspergillus carbonarius is the principal fungal species responsible for ochratoxin A (OTA) contamination of grapes and derived products in the main viticultural regions worldwide. In recent years, co-expressed genes representing a putative-OTA gene cluster were identified, and the deletion of a few of [...] Read more.
Aspergillus carbonarius is the principal fungal species responsible for ochratoxin A (OTA) contamination of grapes and derived products in the main viticultural regions worldwide. In recent years, co-expressed genes representing a putative-OTA gene cluster were identified, and the deletion of a few of them allowed the partial elucidation of the biosynthetic pathway in the fungus. In the putative OTA-gene cluster is additionally present a bZIP transcription factor (AcOTAbZIP), and with this work, A. carbonarius ΔAcOTAbZIP strains were generated to study its functional role. According to phylogenetic analysis, the gene is conserved in the OTA-producing fungi. A Saccharomyces cerevisiae transcription factor binding motif (TFBM) homolog, associated with bZIP transcription factors was present in the A. carbonarius OTA-gene cluster no-coding regions. AcOTAbZIP deletion results in the loss of OTA and the intermediates OTB and OTβ. Additionally, in ΔAcOTAbZIP strains, a down-regulation of AcOTApks, AcOTAnrps, AcOTAp450, and AcOTAhal genes was observed compared to wild type (WT). These results provide evidence of the direct involvement of the AcOTAbZIP gene in the OTA biosynthetic pathway by regulating the involved genes. The loss of OTA biosynthesis ability does not affect fungal development as demonstrated by the comparison of ΔAcOTAbZIP strains and WT strains in terms of vegetative growth and asexual sporulation on three different media. Finally, no statistically significant differences in virulence were observed among ΔAcOTAbZIP strains and WT strains on artificially inoculated grape berries, demonstrating that OTA is not required by A. carbonarius for the pathogenicity process. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
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12 pages, 2588 KiB  
Article
Carbon Catabolite Repression Gene AoCreA Regulates Morphological Development and Ochratoxin A Biosynthesis Responding to Carbon Sources in Aspergillus ochraceus
Toxins 2020, 12(11), 697; https://doi.org/10.3390/toxins12110697 - 03 Nov 2020
Cited by 8 | Viewed by 2063
Abstract
Carbon is one of the most important nutrients for the development and secondary metabolism in fungi. CreA is the major transcriptional factor mediating carbon catabolite repression, which is employed in the utilization of carbon sources. Aspergillus ochraceus contaminates various food and feed containing [...] Read more.
Carbon is one of the most important nutrients for the development and secondary metabolism in fungi. CreA is the major transcriptional factor mediating carbon catabolite repression, which is employed in the utilization of carbon sources. Aspergillus ochraceus contaminates various food and feed containing different carbon sources by producing ochratoxin A (OTA). However, little is known about the function of AoCreA in regulating the morphology and OTA production of A. ochraceus. To give an insight into the mechanism of the carbon sources regulating development of A. ochraceus and OTA production, we have identified AoCreA in A. ochraceus. The homologous recombination strategy was used to generate the AoCreA deletion mutant (ΔAoCreA). We have investigated the morphology and OTA production of the wild type (WT) and ΔAoCreA of A. ochraceus with media containing different carbon sources (glucose, fructose, maltose, D-xylose, D-mannose, acetate, D-galactose, D-mannitol and lactose). ΔAoCreA showed a significant growth and conidiation defect on all media as compared with WT. Glucose and maltose were the most inducing media for OTA production by A. ochraceus, followed by sucrose and the nutrient-rich Yeast Extract Sucrose (YES) and Potato Dextrose Agar (PDA). The deletion of AoCreA led to a drastic reduction of OTA production on all kinds of media except PDA, which was supported by the expression profile of OTA biosynthetic genes. Furthermore, infection studies of ΔAoCreA on oats and pears showed the involvement of AoCreA in the pathogenicity of A. ochraceus. Thus, these results suggest that AoCreA regulates morphological development and OTA biosynthesis in response to carbon sources in A. ochraceus. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
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30 pages, 1466 KiB  
Article
Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach
Toxins 2020, 12(7), 429; https://doi.org/10.3390/toxins12070429 - 29 Jun 2020
Cited by 21 | Viewed by 3972
Abstract
Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, [...] Read more.
Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
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11 pages, 1509 KiB  
Article
Corn Flour Intake, Aflatoxin B1 Exposure, and Risk of Esophageal Precancerous Lesions in a High-Risk Area of Huai’an, China: A Case-Control Study
Toxins 2020, 12(5), 299; https://doi.org/10.3390/toxins12050299 - 06 May 2020
Cited by 13 | Viewed by 2785
Abstract
Aflatoxin B1 (AFB1), which has potent toxicity and carcinogenicity, is a common contaminant of important agricultural commodities. This study aimed to investigate the frequency of corn flour intake and assess the exposure to AFB1 via direct detection of AFB [...] Read more.
Aflatoxin B1 (AFB1), which has potent toxicity and carcinogenicity, is a common contaminant of important agricultural commodities. This study aimed to investigate the frequency of corn flour intake and assess the exposure to AFB1 via direct detection of AFB1 in the diet and serum AFB1 exposure biomarker, so as to evaluate their associations with the risk of esophageal precancerous lesions (EPL). A case-control study based on three-day duplicate diet samples was performed in Huai’an District. One hundred EPL cases and 100 healthy controls were enrolled and required to be age- (±2 years) and gender-matched. The concentration of AFB1 in food samples and the level of serum AFB1-albumin (AFB1-Alb) adduct were quantitatively analyzed. Results showed that corn flour intake was positively associated with serum AFB1-Alb adduct level (p for trend = 0.003), dietary AFB1 exposure (p for trend < 0.001), and the risk of EPL (p for trend = 0.017). Increased serum AFB1-Alb adduct level was associated with an increased risk of EPL as well (p for trend < 0.001). In conclusion, corn flour may be an essential source of AFB1 in Huai’an District, whereas high exposure to AFB1 is likely to be an important risk factor contributing to the progression of EPL. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
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