The<i>Aspergillus</i>Genome Database: multispecies curation and incorporation of RNA-Seq data to improve structural gene annotations

Cerqueira, Gustavo C.; Arnaud, M.; Inglis, Diane O.; Skrzypek, Marek S.; Binkley, Gail; Simison, Matt; Miyasato, Stuart R.; Binkley, Jonathan; Orvis, Joshua; Shah, Prachi; Wymore, Farrell; Sherlock, Gavin; Wortman, Jennifer

doi:10.1093/nar/gkt1029

Cited by 255 publications

(260 citation statements)

References 16 publications

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“…S4), as LaeB seems to regulate ST production transcriptionally as well as potentially through another unidentified pathway. Regarding SntB, the predicted gene model appears to be incorrect in the NCBI database as well as on the Aspergillus Genome Database (60,61). Both databases predict the presence of gene products smaller than the SNT2 homolog in Saccharomyces cerevisiae, A. fumigatus, and A. flavus.…”

Section: Fig 2 Gene Deletions Of Novel Regulators Inmentioning

confidence: 99%

Revitalization of a Forward Genetic Screen Identifies Three New Regulators of Fungal Secondary Metabolism in the Genus Aspergillus

Pfannenstiel

Zhao

Wortman

et al. 2017

mBio

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The study of aflatoxin in Aspergillus spp. has garnered the attention of many researchers due to aflatoxin's carcinogenic properties and frequency as a food and feed contaminant. Significant progress has been made by utilizing the model organism Aspergillus nidulans to characterize the regulation of sterigmatocystin (ST), the penultimate precursor of aflatoxin. A previous forward genetic screen identified 23 A. nidulans mutants involved in regulating ST production. Six mutants were characterized from this screen using classical mapping (five mutations in mcsA) and complementation with a cosmid library (one mutation in laeA). The remaining mutants were backcrossed and sequenced using Illumina and Ion Torrent sequencing platforms. All but one mutant contained one or more sequence variants in predicted open reading frames. Deletion of these genes resulted in identification of mutant alleles responsible for the loss of ST production in 12 of the 17 remaining mutants. Eight of these mutations were in genes already known to affect ST synthesis (laeA, mcsA, fluG, and stcA), while the remaining four mutations (in laeB, sntB, and hamI) were in previously uncharacterized genes not known to be involved in ST production. Deletion of laeB, sntB, and hamI in A. flavus results in loss of aflatoxin production, confirming that these regulators are conserved in the aflatoxigenic aspergilli. This report highlights the multifaceted regulatory mechanisms governing secondary metabolism in Aspergillus. Additionally, these data contribute to the increasing number of studies showing that forward genetic screens of fungi coupled with wholegenome resequencing is a robust and cost-effective technique.IMPORTANCE In a postgenomic world, reverse genetic approaches have displaced their forward genetic counterparts. The techniques used in forward genetics to identify loci of interest were typically very cumbersome and time-consuming, relying on Mendelian traits in model organisms. The current work was pursued not only to identify alleles involved in regulation of secondary metabolism but also to demonstrate a return to forward genetics to track phenotypes and to discover genetic pathways that could not be predicted through a reverse genetics approach. While identification of mutant alleles from whole-genome sequencing has been done before, here we illustrate the possibility of coupling this strategy with a genetic screen

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Section: Fig 2 Gene Deletions Of Novel Regulators Inmentioning

confidence: 99%

Revitalization of a Forward Genetic Screen Identifies Three New Regulators of Fungal Secondary Metabolism in the Genus Aspergillus

Pfannenstiel

Zhao

Wortman

et al. 2017

mBio

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“…The Aspergillus Genome Database (AspGD) collects biologically important information of genomic records, proteins, subcellular localizations, and functions of the genus Aspergillus, predominantly for the A. nidulans, A. fumigatus, A. flavus, A. niger, and A. oryzae species complexes. In addition to analytical tools and multispecies comparison, it provides annotation updates and literature links (44).…”

Section: Online Databases For Taxonomy and Identification Of Pathogenmentioning

confidence: 99%

Online Databases for Taxonomy and Identification of Pathogenic Fungi and Proposal for a Cloud-Based Dynamic Data Network Platform

et al. 2017

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The increase in public online databases dedicated to fungal identification is noteworthy. This can be attributed to improved access to molecular approaches to characterize fungi, as well as to delineate species within specific fungal groups in the last 2 decades, leading to an ever-increasing complexity of taxonomic assortments and nomenclatural reassignments. Thus, well-curated fungal databases with substantial accurate sequence data play a pivotal role for further research and diagnostics in the field of mycology. This minireview aims to provide an overview of currently available online databases for the taxonomy and identification of human and animal-pathogenic fungi and calls for the establishment of a cloudbased dynamic data network platform.

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“…The resulting list was compared with A. fumigatus proteins identified in AspGD (http://www.aspgd.org) with terms ”flavo”, ”flavin”, ”FMN” and ”FAD” [20]. …”

Section: Methodsmentioning

confidence: 99%

Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus

et al. 2018

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Background: Aspergillus fumigatus is the most prevalent airborne fungal pathogen, causing invasive fungal infections mainly in immunosuppressed individuals. Death rates from invasive aspergillosis remain high because of limited treatment options and increasing antifungal resistance. The aim of this study was to identify key fungal-specific genes participating in vitamin B biosynthesis in A. fumigatus. Because these genes are absent in humans they can serve as possible novel targets for antifungal drug development. Methods: By sequence homology we identified, deleted and analysed four key A. fumigatus genes (riboB, panA, pyroA, thiB) involved respectively in the biosynthesis of riboflavin (vitamin B2), pantothenic acid (vitamin B5), pyridoxine (vitamin B6) and thiamine (vitamin B1). Results: Deletion of riboB, panA, pyroA or thiB resulted in respective vitamin auxotrophy. Lack of riboflavin and pantothenic acid biosynthesis perturbed many cellular processes including iron homeostasis. Virulence in murine pulmonary and systemic models of infection was severely attenuated following deletion of riboB and panA, strongly reduced after pyroA deletion and weakly attenuated after thiB deletion. Conclusions: This study reveals the biosynthetic pathways of the vitamins riboflavin and pantothenic acid as attractive targets for novel antifungal therapy. Moreover, the virulence studies with auxotrophic mutants serve to identify the availability of nutrients to pathogens in host niches.Abbreviations: BPS: bathophenanthrolinedisulfonate; BSA: bovine serum albumin; CFU: colony forming unit; -Fe: iron starvation; +Fe: iron sufficiency; hFe: high iron; NRPSs: nonribosomal peptide synthetases; PKSs: polyketide synthaseses; wt: wild type

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TheAspergillusGenome Database: multispecies curation and incorporation of RNA-Seq data to improve structural gene annotations

Cited by 255 publications

References 16 publications

Revitalization of a Forward Genetic Screen Identifies Three New Regulators of Fungal Secondary Metabolism in the Genus Aspergillus

Revitalization of a Forward Genetic Screen Identifies Three New Regulators of Fungal Secondary Metabolism in the Genus Aspergillus

Online Databases for Taxonomy and Identification of Pathogenic Fungi and Proposal for a Cloud-Based Dynamic Data Network Platform

Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus

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