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Yanxia Zhao; Mi-Kyung Lee; Jieyin Lim; Heungyun Moon; Hee-Soo Park; Weifa Zheng; Jae-Hyuk Yu. The putative sensor histidine kinase VadJ coordinates development and sterigmatocystin production in Aspergillus nidulans. Journal of Microbiology 2021, 1 -7.
AMA StyleYanxia Zhao, Mi-Kyung Lee, Jieyin Lim, Heungyun Moon, Hee-Soo Park, Weifa Zheng, Jae-Hyuk Yu. The putative sensor histidine kinase VadJ coordinates development and sterigmatocystin production in Aspergillus nidulans. Journal of Microbiology. 2021; ():1-7.
Chicago/Turabian StyleYanxia Zhao; Mi-Kyung Lee; Jieyin Lim; Heungyun Moon; Hee-Soo Park; Weifa Zheng; Jae-Hyuk Yu. 2021. "The putative sensor histidine kinase VadJ coordinates development and sterigmatocystin production in Aspergillus nidulans." Journal of Microbiology , no. : 1-7.
Cadmium is an exceptionally toxic industrial and environmental pollutant classified as a human carcinogen. In order to provide insight into how we can keep our environment safe from cadmium contamination and prevent the accumulation of it in the food chain, we aim to elucidate how Aspergillus nidulans, one of the most abundant fungi in soil, survives and handles cadmium stress. As AtfA is the main transcription factor governing stress responses in A. nidulans, we examined genome-wide expression responses of wild-type and the atfA null mutant exposed to CdCl2. Both strains showed up-regulation of the crpA Cu2+/Cd2+ pump gene and AN7729 predicted to encode a putative bis(glutathionato)-cadmium transporter, and transcriptional changes associated with elevated intracellular Cys availability leading to the efficient adaptation to Cd2+. Although the deletion of atfA did not alter the cadmium tolerance of the fungus, the cadmium stress response of the mutant differed from that of a reference strain. Promoter and transcriptional analyses of the “Phospho-relay response regulator” genes suggest that the AtfA-dependent regulation of these genes can be relevant in this phenomenon. We concluded that the regulatory network of A. nidulans has a high flexibility allowing the fungus to adapt efficiently to stress both in the presence and absence of this important transcription factor.
Tamás Emri; Barnabás Gila; Károly Antal; Fanni Fekete; Heungyun Moon; Jae-Hyuk Yu; István Pócsi. AtfA-Independent Adaptation to the Toxic Heavy Metal Cadmium in Aspergillus nidulans. Microorganisms 2021, 9, 1433 .
AMA StyleTamás Emri, Barnabás Gila, Károly Antal, Fanni Fekete, Heungyun Moon, Jae-Hyuk Yu, István Pócsi. AtfA-Independent Adaptation to the Toxic Heavy Metal Cadmium in Aspergillus nidulans. Microorganisms. 2021; 9 (7):1433.
Chicago/Turabian StyleTamás Emri; Barnabás Gila; Károly Antal; Fanni Fekete; Heungyun Moon; Jae-Hyuk Yu; István Pócsi. 2021. "AtfA-Independent Adaptation to the Toxic Heavy Metal Cadmium in Aspergillus nidulans." Microorganisms 9, no. 7: 1433.
Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character, and high intracellular concentration, GSH profoundly shapes the redox status of cells.
Barnabás Csaba Gila; Heungyun Moon; Károly Antal; Márton Hajdu; Réka Kovács; Andrea P. Jónás; Tünde Pusztahelyi; Jae-Hyuk Yu; István Pócsi; Tamás Emri. The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans. Applied and Environmental Microbiology 2021, 87, 1 .
AMA StyleBarnabás Csaba Gila, Heungyun Moon, Károly Antal, Márton Hajdu, Réka Kovács, Andrea P. Jónás, Tünde Pusztahelyi, Jae-Hyuk Yu, István Pócsi, Tamás Emri. The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans. Applied and Environmental Microbiology. 2021; 87 (9):1.
Chicago/Turabian StyleBarnabás Csaba Gila; Heungyun Moon; Károly Antal; Márton Hajdu; Réka Kovács; Andrea P. Jónás; Tünde Pusztahelyi; Jae-Hyuk Yu; István Pócsi; Tamás Emri. 2021. "The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans." Applied and Environmental Microbiology 87, no. 9: 1.
The APSES family proteins are transcription factors (TFs) with a basic helix-loop-helix domain, known to regulate growth, development, secondary metabolism, and other biological processes in Aspergillus species. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, five genes predicted to encode APSES TFs are present. Here, we report the characterization of one of these genes, called mbsA (Afu7g05620). The deletion (Δ) of mbsA resulted in significantly decreased hyphal growth and asexual sporulation (conidiation), and lowered mRNA levels of the key conidiation genes abaA, brlA, and wetA. Moreover, ΔmbsA resulted in reduced spore germination rates, elevated sensitivity toward Nikkomycin Z, and significantly lowered transcripts levels of genes associated with chitin synthesis. The mbsA deletion also resulted in significantly reduced levels of proteins and transcripts of genes associated with the SakA MAP kinase pathway. Importantly, the cell wall hydrophobicity and architecture of the ΔmbsA asexual spores (conidia) were altered, notably lacking the rodlet layer on the surface of the ΔmbsA conidium. Comparative transcriptomic analyses revealed that the ΔmbsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes, which was corroborated by elevated levels of GT production in the mutant. While the ΔmbsA mutant produced higher amount of GT, ΔmbsA strains showed reduced virulence in the murine model, likely due to the defective spore integrity. In summary, the putative APSES TF MbsA plays a multiple role in governing growth, development, spore wall architecture, GT production, and virulence, which may be associated with the attenuated SakA signaling pathway.
Yong-Ho Choi; Sang-Cheol Jun; Min-Woo Lee; Jae-Hyuk Yu; Kwang-Soo Shin. Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus. International Journal of Molecular Sciences 2021, 22, 3777 .
AMA StyleYong-Ho Choi, Sang-Cheol Jun, Min-Woo Lee, Jae-Hyuk Yu, Kwang-Soo Shin. Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus. International Journal of Molecular Sciences. 2021; 22 (7):3777.
Chicago/Turabian StyleYong-Ho Choi; Sang-Cheol Jun; Min-Woo Lee; Jae-Hyuk Yu; Kwang-Soo Shin. 2021. "Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus." International Journal of Molecular Sciences 22, no. 7: 3777.
Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. Aspergillus species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs).
Ming-Yueh Wu; Matthew E. Mead; Mi-Kyung Lee; George F. Neuhaus; Donovon A. Adpressa; Julia I. Martien; Ye-Eun Son; Heungyun Moon; Daniel Amador-Noguez; Kap-Hoon Han; Antonis Rokas; Sandra Loesgen; Jae-Hyuk Yu; Hee-Soo Park. Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores. mBio 2021, 12, 1 .
AMA StyleMing-Yueh Wu, Matthew E. Mead, Mi-Kyung Lee, George F. Neuhaus, Donovon A. Adpressa, Julia I. Martien, Ye-Eun Son, Heungyun Moon, Daniel Amador-Noguez, Kap-Hoon Han, Antonis Rokas, Sandra Loesgen, Jae-Hyuk Yu, Hee-Soo Park. Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores. mBio. 2021; 12 (1):1.
Chicago/Turabian StyleMing-Yueh Wu; Matthew E. Mead; Mi-Kyung Lee; George F. Neuhaus; Donovon A. Adpressa; Julia I. Martien; Ye-Eun Son; Heungyun Moon; Daniel Amador-Noguez; Kap-Hoon Han; Antonis Rokas; Sandra Loesgen; Jae-Hyuk Yu; Hee-Soo Park. 2021. "Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores." mBio 12, no. 1: 1.
Phosphorothioate (PT) DNA modifications-in which a nonbonding phosphate oxygen is replaced with sulfur-represent a widespread, horizontally transferred epigenetic system in prokaryotes and have a highly unusual property of occupying only a small fraction of available consensus sequences in a genome. Using Salmonella enterica as a model, we asked a question of fundamental importance: How do the PT-modifying DndA-E proteins select their GPSAAC/GPSTTC targets? Here, we applied innovative analytical, sequencing, and computational tools to discover a novel behavior for DNA-binding proteins: The Dnd proteins are "parked" at the G6mATC Dam methyltransferase consensus sequence instead of the expected GAAC/GTTC motif, with removal of the 6mA permitting extensive PT modification of GATC sites. This shift in modification sites further revealed a surprising constancy in the density of PT modifications across the genome. Computational analysis showed that GAAC, GTTC, and GATC share common features of DNA shape, which suggests that PT epigenetics are regulated in a density-dependent manner partly by DNA shape-driven target selection in the genome.
Jae-Hyuk Yu; Heesoo Park; Wu X; Cao B; Aquino P; Chiu Tp; Chen C; Jiang S; Deng Z; Chen S; Rohs R; Wang L; Galagan Je; Dedon Pc. Faculty Opinions recommendation of Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2021, 117, 1 .
AMA StyleJae-Hyuk Yu, Heesoo Park, Wu X, Cao B, Aquino P, Chiu Tp, Chen C, Jiang S, Deng Z, Chen S, Rohs R, Wang L, Galagan Je, Dedon Pc. Faculty Opinions recommendation of Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2021; 117 (25):1.
Chicago/Turabian StyleJae-Hyuk Yu; Heesoo Park; Wu X; Cao B; Aquino P; Chiu Tp; Chen C; Jiang S; Deng Z; Chen S; Rohs R; Wang L; Galagan Je; Dedon Pc. 2021. "Faculty Opinions recommendation of Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 117, no. 25: 1.
The most common, toxic, and carcinogenic mycotoxins found in human food and animal feed are the aflatoxins (AFs). The U.S. is a leading exporter of various nuts, with a marketing value of $9.1 billion in 2019; the E.U. countries are the major importers of U.S. nuts. In the past few years, border rejections and notifications for U.S. tree nuts and peanuts exported to the E.U. countries have increased due to AF contamination. In this work, we analyzed notifications from the “Rapid Alert System for Food and Feed (RASFF)” on U.S. food and feed products contaminated with mycotoxins, primarily AFs, for the 10-year period 2010–2019. Almost 95% of U.S. mycotoxin RASFF notifications were reported for foods and only 5% for feeds. We found that 98.9% of the U.S. food notifications on mycotoxins were due to the AF contamination in almond, peanut, and pistachio nuts. Over half of these notifications (57.9%) were due to total AF levels greater than the FDA action level in food of 20 ng g−1. The Netherlands issued 27% of the AF notifications for U.S. nuts. Border rejection was reported for more than 78% of AF notifications in U.S. nuts. All U.S. feed notifications on mycotoxins occurred due to the AF contamination. Our research contributes to better understanding the main reasons behind RASFF mycotoxins notifications of U.S. food and feed products destined to E.U. countries. Furthermore, we speculate possible causes of this problem and provide a potential solution that could minimize the number of notifications for U.S. agricultural export market.
Ahmad Alshannaq; Jae-Hyuk Yu. Analysis of E.U. Rapid Alert System (RASFF) Notifications for Aflatoxins in Exported U.S. Food and Feed Products for 2010–2019. Toxins 2021, 13, 90 .
AMA StyleAhmad Alshannaq, Jae-Hyuk Yu. Analysis of E.U. Rapid Alert System (RASFF) Notifications for Aflatoxins in Exported U.S. Food and Feed Products for 2010–2019. Toxins. 2021; 13 (2):90.
Chicago/Turabian StyleAhmad Alshannaq; Jae-Hyuk Yu. 2021. "Analysis of E.U. Rapid Alert System (RASFF) Notifications for Aflatoxins in Exported U.S. Food and Feed Products for 2010–2019." Toxins 13, no. 2: 90.
Compared to the traditional heterogeneous assays, a homogeneous immunoassay is a preferred format for its simplicity. By cloning and isolating luminescent proteins from bioluminescent organisms, bioluminescence has been widely used for various biological applications. In this study, we present the development of a homogeneous luminescence immunoassay (FNanoBiT assay) for detection of fumonisin B1 (FB1), based on the binding of two subunits of an engineered luminescent protein (NanoLuc). For the detection of the mycotoxin FB1 in foods, the anti-fumonisin antibody was conjugated to the large subunit of NanoLuc (FLgBiT), and the FB1 was conjugated to the small subunit (FSmBiT). The conjugates were used for the detection of FB1 in a competitive immunoassay format without the need of a secondary antibody, or washing steps. The developed FNanoBiT assay revealed high specificity toward FB1 with no cross-reactivity with other mycotoxins, and it demonstrated acceptable recovery (higher than 94%) and relative standard deviation from spiked maize samples. Further, the assay was successfully applied for the detection of FB1 in naturally contaminated maize, with a dynamic range of 0.533–6.81 ng mL-1 and a detection limit of 0.079 ng mL-1. The results derived with FNanoBiT assay of all spiked samples showed a strong correlation to those obtained by the High-performance liquid chromatography method. Thus, the FNanoBiT based homogeneous immunoassay could be used as a rapid, and simple tool for the analysis of mycotoxin-contaminated foods.
Tawfiq Alsulami; Nidhi Nath; Rod Flemming; Hui Wang; Wenhui Zhou; Jae-Hyuk Yu. Development of a novel homogeneous immunoassay using the engineered luminescent enzyme NanoLuc for the quantification of the mycotoxin fumonisin B1. Biosensors and Bioelectronics 2020, 177, 112939 .
AMA StyleTawfiq Alsulami, Nidhi Nath, Rod Flemming, Hui Wang, Wenhui Zhou, Jae-Hyuk Yu. Development of a novel homogeneous immunoassay using the engineered luminescent enzyme NanoLuc for the quantification of the mycotoxin fumonisin B1. Biosensors and Bioelectronics. 2020; 177 ():112939.
Chicago/Turabian StyleTawfiq Alsulami; Nidhi Nath; Rod Flemming; Hui Wang; Wenhui Zhou; Jae-Hyuk Yu. 2020. "Development of a novel homogeneous immunoassay using the engineered luminescent enzyme NanoLuc for the quantification of the mycotoxin fumonisin B1." Biosensors and Bioelectronics 177, no. : 112939.
Aspergillus flavus is an agriculturally and medically important filamentous fungus that produces mycotoxins, including aflatoxins, which are potent carcinogens. Here, we generated short- and long-read transcript sequence data from the growth of A. flavus strain NRRL 3357 under both typical and stress conditions to produce a new annotation of its genome.
E. Anne Hatmaker; Xiaofan Zhou; Matthew E. Mead; Heungyun Moon; Jae-Hyuk Yu; Antonis Rokas. Revised Transcriptome-Based Gene Annotation for Aspergillus flavus Strain NRRL 3357. Microbiology Resource Announcements 2020, 9, 1 .
AMA StyleE. Anne Hatmaker, Xiaofan Zhou, Matthew E. Mead, Heungyun Moon, Jae-Hyuk Yu, Antonis Rokas. Revised Transcriptome-Based Gene Annotation for Aspergillus flavus Strain NRRL 3357. Microbiology Resource Announcements. 2020; 9 (49):1.
Chicago/Turabian StyleE. Anne Hatmaker; Xiaofan Zhou; Matthew E. Mead; Heungyun Moon; Jae-Hyuk Yu; Antonis Rokas. 2020. "Revised Transcriptome-Based Gene Annotation for Aspergillus flavus Strain NRRL 3357." Microbiology Resource Announcements 9, no. 49: 1.
The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting of the α, β, and γ subunits. Regulators of G-protein signaling (RGSs) are the key controllers of G-protein signaling pathways. GPCRs, G-proteins, and RGSs are the primary upstream components of the G-protein signaling pathway, and they are highly conserved in most filamentous fungi, playing diverse roles in biological processes. Recent studies characterized the G-protein signaling components in the opportunistic pathogenic fungus Aspergillus fumigatus. In this review, we have summarized the characteristics and functions of GPCRs, G-proteins, and RGSs, and their regulatory roles in governing fungal growth, asexual development, germination, stress tolerance, and virulence in A. fumigatus.
Hee-Soo Park; Min-Ju Kim; Jae-Hyuk Yu; Kwang-Soo Shin. Heterotrimeric G-protein signalers and RGSs in Aspergillus fumigatus. Pathogens 2020, 9, 902 .
AMA StyleHee-Soo Park, Min-Ju Kim, Jae-Hyuk Yu, Kwang-Soo Shin. Heterotrimeric G-protein signalers and RGSs in Aspergillus fumigatus. Pathogens. 2020; 9 (11):902.
Chicago/Turabian StyleHee-Soo Park; Min-Ju Kim; Jae-Hyuk Yu; Kwang-Soo Shin. 2020. "Heterotrimeric G-protein signalers and RGSs in Aspergillus fumigatus." Pathogens 9, no. 11: 902.
McrA is a key transcription factor that functions as a global repressor of fungal secondary metabolism in Aspergillus species. Here, we report that mcrA is one of the VosA-VelB target genes and McrA governs the cellular and metabolic development in Aspergillus nidulans. The deletion of mcrA resulted in a reduced number of conidia and decreased mRNA levels of brlA, the key asexual developmental activator. In addition, the absence of mcrA led to a loss of long-term viability of asexual spores (conidia), which is likely associated with the lack of conidial trehalose and increased β-(1,3)-glucan levels in conidia. In supporting its repressive role, the mcrA deletion mutant conidia contain more amounts of sterigmatocystin and an unknown metabolite than the wild type conidia. While overexpression of mcrA caused the fluffy-autolytic phenotype coupled with accelerated cell death, deletion of mcrA did not fully suppress the developmental defects caused by the lack of the regulator of G-protein signaling protein FlbA. On the contrary to the cellular development, sterigmatocystin production was restored in the ΔflbA ΔmcrA double mutant, and overexpression of mcrA completely blocked the production of sterigmatocystin. Overall, McrA plays a multiple role in governing growth, development, spore viability, and secondary metabolism in A. nidulans.
Mi-Kyung Lee; Ye-Eun Son; Hee-Soo Park; Ahmad Alshannaq; Kap-Hoon Han; Jae-Hyuk Yu. Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans. Scientific Reports 2020, 10, 1 .
AMA StyleMi-Kyung Lee, Ye-Eun Son, Hee-Soo Park, Ahmad Alshannaq, Kap-Hoon Han, Jae-Hyuk Yu. Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans. Scientific Reports. 2020; 10 (1):1.
Chicago/Turabian StyleMi-Kyung Lee; Ye-Eun Son; Hee-Soo Park; Ahmad Alshannaq; Kap-Hoon Han; Jae-Hyuk Yu. 2020. "Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans." Scientific Reports 10, no. 1: 1.
In filamentous fungi, asexual development involves morphological differentiation and metabolic changes leading to the formation of asexual spores. The process of asexual spore formation in Aspergillus is precisely regulated by multiple transcription factors (TFs), including VosA, VelB, and WetA, and these three TFs are key regulators of the formation and maturation of asexual spores (conidia) in Aspergillus including the model fungus Aspergillus nidulans. To gain a mechanistic insight on the complex regulatory roles of these TFs in asexual spores, we conducted genome-wide studies on the expression, protein-DNA interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation-sequencing data have revealed that the three TFs directly or indirectly regulate the expression of genes associated with spore-wall formation/integrity, asexual development, and secondary metabolism. In addition, metabolomics analyses of wild-type and mutant conidia indicate that these three TFs regulate a diverse array of primary and secondary metabolism. In summary, WetA, VosA, and VelB play inter-dependent and distinct roles governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia. Importance Filamentous fungi produce a vast number of asexual spores that act as reproductive and propagator cells. These spores affect humans, due to the infectious or allergenic nature of the propagule. Aspergillus species produce asexual spores called conidia and their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by spore-specific transcription factors. To understand the underlying global regulatory programs and cellular outcomes associated with conidia formation, functional genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans. Our results show that the fungus specific WetA/VosA/VelB transcription factors govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the genetic regulatory networks about how morphological developments and metabolic changes are coordinated in fungi. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin-producer Aspergillus flavus.
Ming-Yueh Wu; Matthew E. Mead; Mi-Kyung Lee; George F. Neuhaus; Donovon A. Adpressa; Julia Isabel Martien; Ye-Eun Son; Heungyun Moon; Daniel Amador-Noguez; Kap-Hoon Han; Antonis Rokas; Sandra Loesgen; Jae-Hyuk Yu; Hee-Soo Park. Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans asexual spores. 2020, 1 .
AMA StyleMing-Yueh Wu, Matthew E. Mead, Mi-Kyung Lee, George F. Neuhaus, Donovon A. Adpressa, Julia Isabel Martien, Ye-Eun Son, Heungyun Moon, Daniel Amador-Noguez, Kap-Hoon Han, Antonis Rokas, Sandra Loesgen, Jae-Hyuk Yu, Hee-Soo Park. Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans asexual spores. . 2020; ():1.
Chicago/Turabian StyleMing-Yueh Wu; Matthew E. Mead; Mi-Kyung Lee; George F. Neuhaus; Donovon A. Adpressa; Julia Isabel Martien; Ye-Eun Son; Heungyun Moon; Daniel Amador-Noguez; Kap-Hoon Han; Antonis Rokas; Sandra Loesgen; Jae-Hyuk Yu; Hee-Soo Park. 2020. "Transcriptomic, protein-DNA interaction, and metabolomic studies of VosA, VelB, and WetA in Aspergillus nidulans asexual spores." , no. : 1.
Some aspergilli are among the most cosmopolitan and ecologically dominant fungal species. One pillar of their success is their complex life cycle, which creates specialized cell types for versatile dispersal and regenesis. One of these cell types is unique to aspergilli-the Hülle cells. Despite being known for over a century, the biological and ecological roles of Hülle cells remain largely speculative. Previously reported data on in vivo Hülle cell formation and localization have been conflicting. Our quantification reveals that Hülle cells can occur at all locations on hyphae and that they show cellular activity similar to that seen with adjacent hyphae, indicating that they develop as intricate parts of hyphal tissue. In addition, we show that during sexual development associated with two parental strains, the typically multinucleate Hülle cells can inherit nuclei from both parents, indicating that they may serve as genetic backups. We provide an easy, reproducible method to study Hülle cell biology and germination with which we investigate the 90-year-old puzzle of whether and how Hülle cells germinate. We present clear evidence for the germination of Hülle cells, and we show that Hülle cells grow hyphae that develop into a spore-producing colony. Finally, we show that Hülle cell-derived colonies produce conidiospores faster than spore-derived colonies, providing evidence for an as-yet-undescribed developmental shortcut program in Aspergillus nidulans We propose that Hülle cells represent a unique cell type as specialized hypha-derived sexual tissue with a nucleus storage function and may act as fungal backup stem cells under highly destructive conditions.IMPORTANCE The in vivo identification of Hülle cells in cases of aspergillosis infections in animals and humans illustrates their biological relevance and suggests that they might be involved in pathogenicity. It is striking that aspergilli have developed and maintained a multinucleate nurse cell that is presumably energy-intensive to produce and is usually found only in higher eukaryotes. Our findings shed light on how the understudied Hülle cells might contribute to the success of aspergilli by acting not only as nurse cells under detrimental conditions (sexual development) but also as fungal backup stem cells with the capacity to produce genetically diverse spores in an accelerated manner, thereby substantially contributing to survival in response to predator attack or under otherwise severely destructive conditions. Our study solved the 90-year-old puzzle of Hülle cell germination and provides easy, reproducible methods that will facilitate future studies on biological and ecological roles of Hülle cells in aspergilli.Copyright © 2020 Troppens et al.
Jae-Hyuk Yu; Heesoo Park; Troppens Dm; Köhler Am; Schlüter R; Hoppert M; Gerke J; Braus Gh. Faculty Opinions recommendation of Hülle Cells of Aspergillus nidulans with Nuclear Storage and Developmental Backup Functions Are Reminiscent of Multipotent Stem Cells. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2020, 11, 1 .
AMA StyleJae-Hyuk Yu, Heesoo Park, Troppens Dm, Köhler Am, Schlüter R, Hoppert M, Gerke J, Braus Gh. Faculty Opinions recommendation of Hülle Cells of Aspergillus nidulans with Nuclear Storage and Developmental Backup Functions Are Reminiscent of Multipotent Stem Cells. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2020; 11 (4):1.
Chicago/Turabian StyleJae-Hyuk Yu; Heesoo Park; Troppens Dm; Köhler Am; Schlüter R; Hoppert M; Gerke J; Braus Gh. 2020. "Faculty Opinions recommendation of Hülle Cells of Aspergillus nidulans with Nuclear Storage and Developmental Backup Functions Are Reminiscent of Multipotent Stem Cells." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 11, no. 4: 1.
Cytochrome P450 monooxygenases (CYPs/P450s) are well known for their role in organisms’ primary and secondary metabolism. Among 20 P450s of the tuberculosis-causing Mycobacterium tuberculosis H37Rv, CYP128A1 is particularly important owing to its involvement in synthesizing electron transport molecules such as menaquinone-9 (MK9). This study employs different in silico approaches to understand CYP128 P450 family’s distribution and structural aspects. Genome data-mining of 4250 mycobacterial species has revealed the presence of 2674 CYP128 P450s in 2646 mycobacterial species belonging to six different categories. Contrast features were observed in the CYP128 gene distribution, subfamily patterns, and characteristics of the secondary metabolite biosynthetic gene cluster (BGCs) between M. tuberculosis complex (MTBC) and other mycobacterial category species. In all MTBC species (except one) CYP128 P450s belong to subfamily A, whereas subfamily B is predominant in another four mycobacterial category species. Of CYP128 P450s, 78% was a part of BGCs with CYP124A1, or together with CYP124A1 and CYP121A1. The CYP128 family ranked fifth in the conservation ranking. Unique amino acid patterns are present at the EXXR and CXG motifs. Molecular dynamic simulation studies indicate that the CYP128A1 bind to MK9 with the highest affinity compared to the azole drugs analyzed. This study provides comprehensive comparative analysis and structural insights of CYP128A1 in M. tuberculosis.
Nokwanda Samantha Ngcobo; Zinhle Edith Chiliza; Wanping Chen; Jae-Hyuk Yu; David R. Nelson; Jack A. Tuszynski; Jordane Preto; Khajamohiddin Syed. Comparative Analysis, Structural Insights, and Substrate/Drug Interaction of CYP128A1 in Mycobacterium tuberculosis. International Journal of Molecular Sciences 2020, 21, 4816 .
AMA StyleNokwanda Samantha Ngcobo, Zinhle Edith Chiliza, Wanping Chen, Jae-Hyuk Yu, David R. Nelson, Jack A. Tuszynski, Jordane Preto, Khajamohiddin Syed. Comparative Analysis, Structural Insights, and Substrate/Drug Interaction of CYP128A1 in Mycobacterium tuberculosis. International Journal of Molecular Sciences. 2020; 21 (14):4816.
Chicago/Turabian StyleNokwanda Samantha Ngcobo; Zinhle Edith Chiliza; Wanping Chen; Jae-Hyuk Yu; David R. Nelson; Jack A. Tuszynski; Jordane Preto; Khajamohiddin Syed. 2020. "Comparative Analysis, Structural Insights, and Substrate/Drug Interaction of CYP128A1 in Mycobacterium tuberculosis." International Journal of Molecular Sciences 21, no. 14: 4816.
Unraveling the role of cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolate proteins present in living and non-living entities, in secondary metabolite synthesis is gaining momentum. In this direction, in this study, we analyzed the genomes of 203 Streptomyces species for P450s and unraveled their association with secondary metabolism. Our analyses revealed the presence of 5460 P450s, grouped into 253 families and 698 subfamilies. The CYP107 family was found to be conserved and highly populated in Streptomyces and Bacillus species, indicating its key role in the synthesis of secondary metabolites. Streptomyces species had a higher number of P450s than Bacillus and cyanobacterial species. The average number of secondary metabolite biosynthetic gene clusters (BGCs) and the number of P450s located in BGCs were higher in Streptomyces species than in Bacillus, mycobacterial, and cyanobacterial species, corroborating the superior capacity of Streptomyces species for generating diverse secondary metabolites. Functional analysis via data mining confirmed that many Streptomyces P450s are involved in the biosynthesis of secondary metabolites. This study was the first of its kind to conduct a comparative analysis of P450s in such a large number (203) of Streptomyces species, revealing the P450s’ association with secondary metabolite synthesis in Streptomyces species. Future studies should include the selection of Streptomyces species with a higher number of P450s and BGCs and explore the biotechnological value of secondary metabolites they produce.
Fanele Cabangile Mnguni; Tiara Padayachee; Wanping Chen; Dominik Gront; Jae-Hyuk Yu; David R. Nelson; Khajamohiddin Syed. More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium. International Journal of Molecular Sciences 2020, 21, 4814 .
AMA StyleFanele Cabangile Mnguni, Tiara Padayachee, Wanping Chen, Dominik Gront, Jae-Hyuk Yu, David R. Nelson, Khajamohiddin Syed. More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium. International Journal of Molecular Sciences. 2020; 21 (13):4814.
Chicago/Turabian StyleFanele Cabangile Mnguni; Tiara Padayachee; Wanping Chen; Dominik Gront; Jae-Hyuk Yu; David R. Nelson; Khajamohiddin Syed. 2020. "More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium." International Journal of Molecular Sciences 21, no. 13: 4814.
Bacteria have evolved diverse mechanisms to fend off predation by bacteriophages. We previously identified the Dnd system, which uses DndABCDE to insert sulfur into the DNA backbone as a double-stranded phosphorothioate (PT) modification, and DndFGH, a restriction component. Here, we describe an unusual SspABCD-SspE PT system in Vibrio cyclitrophicus, Escherichia coli and Streptomyces yokosukanensis, which has distinct genetic organization, biochemical functions and phenotypic behaviour. SspABCD confers single-stranded and high-frequency PTs with SspB acting as a nickase and possibly introducing nicks to facilitate sulfur incorporation. Strikingly, SspABCD coupled with SspE provides protection against phages in unusual ways: (1) SspE senses sequence-specific PTs by virtue of its PT-stimulated NTPase activity to exert its anti-phage activity, and (2) SspE inhibits phage propagation by introducing nicking damage to impair phage DNA replication. These results not only expand our knowledge about the diversity and functions of DNA PT modification but also enhance our understanding of the known arsenal of defence systems.
Jae-Hyuk Yu; Heesoo Park; Xiong X; Wu G; Wei Y; Liu L; Zhang Y; Su R; Jiang X; Li M; Gao H; Tian X; Hu L; Chen S; Tang Y; Jiang S; Huang R; Li Z; Wang Y; Deng Z; Wang J; Dedon Pc; Wang L. Faculty Opinions recommendation of SspABCD-SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2020, 1 .
AMA StyleJae-Hyuk Yu, Heesoo Park, Xiong X, Wu G, Wei Y, Liu L, Zhang Y, Su R, Jiang X, Li M, Gao H, Tian X, Hu L, Chen S, Tang Y, Jiang S, Huang R, Li Z, Wang Y, Deng Z, Wang J, Dedon Pc, Wang L. Faculty Opinions recommendation of SspABCD-SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2020; ():1.
Chicago/Turabian StyleJae-Hyuk Yu; Heesoo Park; Xiong X; Wu G; Wei Y; Liu L; Zhang Y; Su R; Jiang X; Li M; Gao H; Tian X; Hu L; Chen S; Tang Y; Jiang S; Huang R; Li Z; Wang Y; Deng Z; Wang J; Dedon Pc; Wang L. 2020. "Faculty Opinions recommendation of SspABCD-SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature , no. : 1.
The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited. We reasoned that clinically relevant antifungal resistance could derive from transcriptional rewiring, promoting drug resistance without concomitant reductions in pathogenicity. Here we report a genome-wide annotation of transcriptional regulators in A. fumigatus and construction of a library of 484 transcription factor null mutants. We identify 12 regulators that have a demonstrable role in itraconazole susceptibility and show that loss of the negative cofactor 2 complex leads to resistance, not only to the azoles but also the salvage therapeutics amphotericin B and terbinafine without significantly affecting pathogenicity.
Jae-Hyuk Yu; Heesoo Park; Furukawa T; Van Rhijn N; Fraczek M; Gsaller F; Davies E; Carr P; Gago S; Fortune-Grant R; Rahman S; Gilsenan Jm; Houlder E; Kowalski Ch; Raj S; Paul S; Cook P; Parker Je; Kelly S; Cramer Ra; Latgé JP; Moye-Rowley S; Bignell E; Bowyer P; Bromley Mj. Faculty Opinions recommendation of The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2020, 11, 1 .
AMA StyleJae-Hyuk Yu, Heesoo Park, Furukawa T, Van Rhijn N, Fraczek M, Gsaller F, Davies E, Carr P, Gago S, Fortune-Grant R, Rahman S, Gilsenan Jm, Houlder E, Kowalski Ch, Raj S, Paul S, Cook P, Parker Je, Kelly S, Cramer Ra, Latgé JP, Moye-Rowley S, Bignell E, Bowyer P, Bromley Mj. Faculty Opinions recommendation of The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2020; 11 (1):1.
Chicago/Turabian StyleJae-Hyuk Yu; Heesoo Park; Furukawa T; Van Rhijn N; Fraczek M; Gsaller F; Davies E; Carr P; Gago S; Fortune-Grant R; Rahman S; Gilsenan Jm; Houlder E; Kowalski Ch; Raj S; Paul S; Cook P; Parker Je; Kelly S; Cramer Ra; Latgé JP; Moye-Rowley S; Bignell E; Bowyer P; Bromley Mj. 2020. "Faculty Opinions recommendation of The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 11, no. 1: 1.
Culture methods supplemented with high-performance liquid chromatography (HPLC) technique provide a rapid and simple tool for detecting levels of aflatoxins (AFs) produced by fungi. This study presents a robust method for simultaneous quantification of aflatoxin (AF) B1, B2, G1, and G2 levels in several fungal cultivation states: submerged shake culture, liquid slant culture, and solid-state culture. The recovery of the method was evaluated by spiking a mixture of AFs at several concentrations to the test medium. The applicability of the method was evaluated by using aflatoxigenic and non-aflatoxigenic Aspergilli. A HPLC coupled with the diode array (DAD) and fluorescence (FLD) detectors was used to determine the presence and amounts of AFs. Both detectors showed high sensitivity in detecting spiked AFs or AFs produced in situ by toxigenic fungi. Our methods showed 76%–88% recovery from medium spiked with 2.5, 10, 50, 100, and 500 ng/mL AFs. The limit of quantification (LOQ) for AFs were 2.5 to 5.0 ng/mL with DAD and 0.025 to 2.5 ng/mL with FLD. In this work, we described in detail a protocol, which can be considered the foremost and only verified method, to extract, detect, and quantify AFs employing both aflatoxigenic and non-toxigenic Aspergilli.
Ahmad F. Alshannaq; Jae-Hyuk Yu. A Liquid Chromatographic Method for Rapid and Sensitive Analysis of Aflatoxins in Laboratory Fungal Cultures. Toxins 2020, 12, 93 .
AMA StyleAhmad F. Alshannaq, Jae-Hyuk Yu. A Liquid Chromatographic Method for Rapid and Sensitive Analysis of Aflatoxins in Laboratory Fungal Cultures. Toxins. 2020; 12 (2):93.
Chicago/Turabian StyleAhmad F. Alshannaq; Jae-Hyuk Yu. 2020. "A Liquid Chromatographic Method for Rapid and Sensitive Analysis of Aflatoxins in Laboratory Fungal Cultures." Toxins 12, no. 2: 93.
The short‐lived hydrophobic gas nitric oxide (NO) is a broadly conserved signaling molecule in all domains of life, including the ubiquitous and versatile filamentous fungi (molds). Several studies have suggested that NO plays a vast and diverse signaling role in molds. In this review, we summarize NO‐mediated signaling and the biosynthesis and degradation of NO in molds, and highlight the recent advances in understanding the NO‐mediated regulation of morphological and physiological processes throughout the fungal life cycle. In particular, we describe the role of NO in molds as a signaling molecule that modulates asexual and sexual development, the formation of infection body appressorium, and the production of secondary metabolites (SMs). In addition, we also summarize NO detoxification and protective mechanisms against nitrooxidative stress.
Yanxia Zhao; Jieyin Lim; Jianyang Xu; Jae‐Hyuk Yu; Weifa Zheng. Nitric oxide as a developmental and metabolic signal in filamentous fungi. Molecular Microbiology 2020, 113, 872 -882.
AMA StyleYanxia Zhao, Jieyin Lim, Jianyang Xu, Jae‐Hyuk Yu, Weifa Zheng. Nitric oxide as a developmental and metabolic signal in filamentous fungi. Molecular Microbiology. 2020; 113 (5):872-882.
Chicago/Turabian StyleYanxia Zhao; Jieyin Lim; Jianyang Xu; Jae‐Hyuk Yu; Weifa Zheng. 2020. "Nitric oxide as a developmental and metabolic signal in filamentous fungi." Molecular Microbiology 113, no. 5: 872-882.
The prokaryotic phylum Cyanobacteria are some of the oldest known photosynthetic organisms responsible for the oxygenation of the earth. Cyanobacterial species have been recognised as a prosperous source of bioactive secondary metabolites with antibacterial, antiviral, antifungal and/or anticancer activities. Cytochrome P450 monooxygenases (CYPs/P450s) contribute to the production and diversity of various secondary metabolites. To better understand the metabolic potential of cyanobacterial species, we have carried out comprehensive analyses of P450s, predicted secondary metabolite biosynthetic gene clusters (BGCs), and P450s located in secondary metabolite BGCs. Analysis of the genomes of 114 cyanobacterial species identified 341 P450s in 88 species, belonging to 36 families and 79 subfamilies. In total, 770 secondary metabolite BGCs were found in 103 cyanobacterial species. Only 8% of P450s were found to be part of BGCs. Comparative analyses with other bacteria Bacillus, Streptomyces and mycobacterial species have revealed a lower number of P450s and BGCs and a percentage of P450s forming part of BGCs in cyanobacterial species. A mathematical formula presented in this study revealed that cyanobacterial species have the highest gene-cluster diversity percentage compared to Bacillus and mycobacterial species, indicating that these diverse gene clusters are destined to produce different types of secondary metabolites. The study provides fundamental knowledge of P450s and those associated with secondary metabolism in cyanobacterial species, which may illuminate their value for the pharmaceutical and cosmetics industries.
Makhosazana Jabulile Khumalo; Nomfundo Nzuza; Tiara Padayachee; Wanping Chen; Jae-Hyuk Yu; David R. Nelson; Khajamohiddin Syed. Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria. International Journal of Molecular Sciences 2020, 21, 656 .
AMA StyleMakhosazana Jabulile Khumalo, Nomfundo Nzuza, Tiara Padayachee, Wanping Chen, Jae-Hyuk Yu, David R. Nelson, Khajamohiddin Syed. Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria. International Journal of Molecular Sciences. 2020; 21 (2):656.
Chicago/Turabian StyleMakhosazana Jabulile Khumalo; Nomfundo Nzuza; Tiara Padayachee; Wanping Chen; Jae-Hyuk Yu; David R. Nelson; Khajamohiddin Syed. 2020. "Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria." International Journal of Molecular Sciences 21, no. 2: 656.