144 research outputs found
Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence Across Aspergillus Species
No full textA portrait of budding yeasts: A symbol of the arts, sciences and a whole greater than the sum of its parts
No full textNutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner
No full textOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.frontiersin.org/articles/10.3389/fmicb.2019.00854/fullAcquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner.JO was supported in part by institutional startup funds and in part through the Dartmouth Lung Biology Center for Molecular, Cellular, and Translational Research grant P30 GM106394 (PI: Bruce A. Stanton) and Center for Molecular, Cellular, and Translational Immunological Research grant P30 GM103415 (PI: William R. Green). FA was supported by a FAPESP young researcher fellowship (2016/03322-7). LR was supported by a FAPESP young researcher fellowship (2017/14159-2). JS was supported by the Graduate Program in Biological Sciences at Vanderbilt University and AR was supported, in part, by the National Science Foundation (DEB-1442113), the Vanderbilt Discovery Grant Program, the Burroughs Wellcome Fund, and the Guggenheim Foundation
Copy Number Variation in Fungi and Its Implications for Wine Yeast Genetic Diversity and Adaptation
No full textIn recent years, copy number (CN) variation has emerged as a new and significant source of genetic polymorphisms contributing to the phenotypic diversity of populations. CN variants are defined as genetic loci that, due to duplication and deletion, vary in their number of copies across individuals in a population. CN variants range in size from 50 base pairs to whole chromosomes, can influence gene activity, and are associated with a wide range of phenotypes in diverse organisms, including the budding yeast Saccharomyces cerevisiae. In this review, we introduce CN variation, discuss the genetic and molecular mechanisms implicated in its generation, how they can contribute to genetic and phenotypic diversity in fungal populations, and consider how CN variants may influence wine yeast adaptation in fermentation-related processes. In particular, we focus on reviewing recent work investigating the contribution of changes in CN of fermentation-related genes in yeast wine strains and offer notable illustrations of such changes, including the high levels of CN variation among the CUP genes, which confer resistance to copper, a metal with fungicidal properties, and the preferential deletion and duplication of the MAL1 and MAL3 loci, respectively, which are responsible for metabolizing maltose and sucrose. Based on the available data, we propose that CN variation is a substantial dimension of yeast genetic diversity that occurs largely independent of single nucleotide polymorphisms. As such, CN variation harbors considerable potential for understanding and manipulating yeast strains in the wine fermentation environment and beyond
The dawn of relaxed phylogenetics.
No full textTracing the history of evolution across time is a primary goal of evolutionary biology. The 2006 publication of a landmark study on relaxed phylogenetics in PLOS Biology enabled biologists to shed light on evolution's tempo and shaped the future of evolutionary studies
Copy number variation in fungi and its implications for wine yeast genetic diversity and adaptation
No full textAbstractIn recent years, copy number (CN) variation has emerged as a new and significant source of genetic polymorphisms contributing to the phenotypic diversity of populations. CN variants are defined as genetic loci that, due to duplication and deletion, vary in their number of copies across individuals in a population. CN variants range in size from 50 base pairs to whole chromosomes, can influence gene activity, and are associated with a wide range of phenotypes in diverse organisms, including the budding yeastSaccharomyces cerevisiae.In this review, we introduce CN variation, discuss the genetic and molecular mechanisms implicated in its generation, how they can contribute to genetic and phenotypic diversity in fungal populations, and consider how CN variants may influence wine yeast adaptation in fermentation-related processes. In particular, we focus on reviewing recent work investigating the contribution of changes in CN of fermentation-related genes associated with the adaptation and domestication of yeast wine strains and offer notable illustrations of such changes, including the high levels of CN variation among theCUPgenes, which confer resistance to copper, and the preferential deletion and duplication of theMALIandMAL3loci, respectively, which are responsible for metabolizing maltose and sucrose. Based on the available data, we propose that CN variation is a substantial dimension of yeast genetic diversity that occurs largely independent of single nucleotide polymorphisms. As such, CN variation harbors considerable potential for understanding and manipulating yeast strains in the wine fermentation environment and beyond.</jats:p
Into the wild: new yeast genomes from natural environments and new tools for their analysis
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in FEMS Yeast Research following peer review. The version of record "D Libkind, D Peris, F A Cubillos, J L Steenwyk, D A Opulente, Q K Langdon, A Rokas, C T Hittinger, Into the wild: new yeast genomes from natural environments and new tools for their analysis, FEMS Yeast Research, Volume 20, Issue 2, March 2020, foaa008" is available online at: https://doi.org/10.1093/femsyr/foaa008Genomic studies of yeasts from the wild have increased considerably in the past few years. This revolution has been fueled by advances in high-throughput sequencing technologies and a better understanding of yeast ecology and phylogeography, especially for biotechnologically important species. The present review aims to first introduce new bioinformatic tools available for the generation and analysis of yeast genomes. We also assess the accumulated genomic data of wild isolates of industrially relevant species, such as Saccharomyces spp., which provide unique opportunities to further investigate the domestication processes associated with the fermentation industry and opportunistic pathogenesis. The availability of genome sequences of other less conventional yeasts obtained from the wild has also increased substantially, including representatives of the phyla Ascomycota (e.g. Hanseniaspora) and Basidiomycota (e.g. Phaffia). Here, we review salient examples of both fundamental and applied research that demonstrate the importance of continuing to sequence and analyze genomes of wild yeasts.DL has been funded through CONICET (PIP11220130100392CO) and Universidad Nacional del Comahue (B199). Research in AR's lab has been funded through a National Science Foundation grant (DEB-1442113); JLS and AR have also received funding by the Howard Hughes Medical Institute through the James H. Gilliam Fellowships for Advanced Study program. CTH has been funded through the National Science Foundation (DEB-1442148), USDA National Institute of Food and Agriculture (Hatch Project 1020204), and DOE Great Lakes Bioenergy Research Center (DE-SC0018409). CTH is a Pew Scholar in the Biomedical Sciences and a H. I. Romnes Faculty Fellow, supported by the Pew Charitable Trusts and Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation, respectively. DP is a Marie Sklodowska-Curie fellow of the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 747775).Peer reviewe
Know the enemy and know yourself: Addressing cryptic fungal pathogens of humans and beyond.
No full textA Robust Phylogenomic Time Tree for Biotechnologically and Medically Important Fungi in the Genera Aspergillus and Penicillium
No full textUnderstanding the evolution of traits across technologically and medically significant fungi requires a robust phylogeny. Even though species in the Aspergillus and Penicillium genera (family Aspergillaceae, class Eurotiomycetes) are some of the most significant technologically and medically relevant fungi, we still lack a genome-scale phylogeny of the lineage or knowledge of the parts of the phylogeny that exhibit conflict among analyses. Here, we used a phylogenomic approach to infer evolutionary relationships among 81 genomes that span the diversity of Aspergillus and Penicillium species, to identify conflicts in the phylogeny, and to determine the likely underlying factors of the observed conflicts. Using a data matrix comprised of 1,668 genes, we found that while most branches of the phylogeny of the Aspergillaceae are robustly supported and recovered irrespective of method of analysis, a few exhibit various degrees of conflict among our analyses. Further examination of the observed conflict revealed that it largely stems from incomplete lineage sorting and hybridization or introgression. Our analyses provide a robust and comprehensive evolutionary genomic roadmap for this important lineage, which will facilitate the examination of the diverse technologically and medically relevant traits of these fungi in an evolutionary context.The filamentous fungal family Aspergillaceae contains >1,000 known species, mostly in the genera Aspergillus and Penicillium. Several species are used in the food, biotechnology, and drug industries (e.g., Aspergillus oryzae and Penicillium camemberti), while others are dangerous human and plant pathogens (e.g., Aspergillus fumigatus and Penicillium digitatum). To infer a robust phylogeny and pinpoint poorly resolved branches and their likely underlying contributors, we used 81 genomes spanning the diversity of Aspergillus and Penicillium to construct a 1,668-gene data matrix. Phylogenies of the nucleotide and amino acid versions of this full data matrix as well as of several additional data matrices were generated using three different maximum likelihood schemes (i.e., gene-partitioned, unpartitioned, and coalescence) and using both site-homogenous and site-heterogeneous models (total of 64 species-level phylogenies). Examination of the topological agreement among these phylogenies and measures of internode certainty identified 11/78 (14.1%) bipartitions that were incongruent and pinpointed the likely underlying contributing factors, which included incomplete lineage sorting, hidden paralogy, hybridization or introgression, and reconstruction artifacts associated with poor taxon sampling. Relaxed molecular clock analyses suggest that Aspergillaceae likely originated in the lower Cretaceous and that the Aspergillus and Penicillium genera originated in the upper Cretaceous. Our results shed light on the ongoing debate on Aspergillus systematics and taxonomy and provide a robust evolutionary and temporal framework for comparative genomic analyses in Aspergillaceae. More broadly, our approach provides a general template for phylogenomic identification of resolved and contentious branches in densely genome-sequenced lineages across the tree of life
Solu : a cloud platform for real-time genomic pathogen surveillance
No full textBackgroundGenomic surveillance is extensively used for tracking public health outbreaks and healthcare-associated pathogens. Despite advancements in bioinformatics pipelines, there are still significant challenges in terms of infrastructure, expertise, and security when it comes to continuous surveillance. The existing pipelines often require the user to set up and manage their own infrastructure and are not designed for continuous surveillance that demands integration of new and regularly generated sequencing data with previous analyses. Additionally, academic projects often do not meet the privacy requirements of healthcare providers.ResultsWe present Solu, a cloud-based platform that integrates genomic data into a real-time, privacy-focused surveillance system.EvaluationSolu's accuracy for taxonomy assignment, antimicrobial resistance genes, and phylogenetics was comparable to established pathogen surveillance pipelines. In some cases, Solu identified antimicrobial resistance genes that were previously undetected. Together, these findings demonstrate the efficacy of our platform.ConclusionsBy enabling reliable, user-friendly, and privacy-focused genomic surveillance, Solu has the potential to bridge the gap between cutting-edge research and practical, widespread application in healthcare settings. The platform is available for free academic use at https://platform.solugenomics.com
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