The Experts below are selected from a list of 147654 Experts worldwide ranked by ideXlab platform
Sandrine Chabas - One of the best experts on this subject based on the ideXlab platform.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5′ end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ∼60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species. The bacterium Helicobacter pylori infects about half the Human population, thriving in the acid conditions of the stomach. Most carriers are asymptomatic, but some suffer inflammation, ulcers and gastric cancer. Now, using a novel approach that selects for the 5' ends of primary transcripts, the 'primary transcriptome' — predominantly the unprocessed messenger RNAs and small non-coding RNAs — has been determined for H. pylori in a variety of growth conditions. With the genome sequence and protein interactome previously published, this work provides the third global reference data set for the widely used Helicobacter strain 26695. The transcriptome of Helicobacter pylori, an important Human Pathogen involved in gastric ulcers and cancer, is presented. The approach establishes a model for mapping and annotating the primary transcriptomes of many living species.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
Fabien Darfeuille - One of the best experts on this subject based on the ideXlab platform.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5′ end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ∼60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species. The bacterium Helicobacter pylori infects about half the Human population, thriving in the acid conditions of the stomach. Most carriers are asymptomatic, but some suffer inflammation, ulcers and gastric cancer. Now, using a novel approach that selects for the 5' ends of primary transcripts, the 'primary transcriptome' — predominantly the unprocessed messenger RNAs and small non-coding RNAs — has been determined for H. pylori in a variety of growth conditions. With the genome sequence and protein interactome previously published, this work provides the third global reference data set for the widely used Helicobacter strain 26695. The transcriptome of Helicobacter pylori, an important Human Pathogen involved in gastric ulcers and cancer, is presented. The approach establishes a model for mapping and annotating the primary transcriptomes of many living species.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
Jeremy Reignier - One of the best experts on this subject based on the ideXlab platform.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5′ end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ∼60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species. The bacterium Helicobacter pylori infects about half the Human population, thriving in the acid conditions of the stomach. Most carriers are asymptomatic, but some suffer inflammation, ulcers and gastric cancer. Now, using a novel approach that selects for the 5' ends of primary transcripts, the 'primary transcriptome' — predominantly the unprocessed messenger RNAs and small non-coding RNAs — has been determined for H. pylori in a variety of growth conditions. With the genome sequence and protein interactome previously published, this work provides the third global reference data set for the widely used Helicobacter strain 26695. The transcriptome of Helicobacter pylori, an important Human Pathogen involved in gastric ulcers and cancer, is presented. The approach establishes a model for mapping and annotating the primary transcriptomes of many living species.
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the primary transcriptome of the major Human Pathogen helicobacter pylori
Nature, 2010Co-Authors: Cynthia M Sharma, Steve Hoffmann, Fabien Darfeuille, Jeremy Reignier, Sven Findeis, Alexandra Sittka, Sandrine ChabasAbstract:Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent Human Pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
Antonis Rokas - One of the best experts on this subject based on the ideXlab platform.
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gliotoxin a known virulence factor in the major Human Pathogen aspergillus fumigatus is also biosynthesized by its nonPathogenic relative aspergillus fischeri
Mbio, 2020Co-Authors: Sonja L Knowles, Matthew E Mead, Lilian Pereira Silva, Huzefa A Raja, Jacob L Steenwyk, Nicholas H Oberlies, Gustavo H Goldma, Antonis RokasAbstract:ABSTRACT Aspergillus fumigatus is a major opportunistic Human Pathogen. Multiple traits contribute to A. fumigatus Pathogenicity, including its ability to produce specific secondary metabolites, such as gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that inactivate gliotoxin biosynthesis (or secondary metabolism in general) attenuate A. fumigatus virulence. The genome of Aspergillus fischeri, a very close nonPathogenic relative of A. fumigatus, contains a biosynthetic gene cluster that is homologous to the A. fumigatus gliotoxin cluster. However, A. fischeri is not known to produce gliotoxin. To gain further insight into the similarities and differences between the major Pathogen A. fumigatus and the nonPathogen A. fischeri, we examined whether A. fischeri strain NRRL 181 biosynthesizes gliotoxin and whether the production of secondary metabolites influences the virulence profile of A. fischeri. We found that A. fischeri biosynthesizes gliotoxin under the same conditions as A. fumigatus. However, whereas loss of laeA, a master regulator of secondary metabolite production (including gliotoxin biosynthesis), has previously been shown to reduce A. fumigatus virulence, we found that laeA loss (and loss of secondary metabolite production) in A. fischeri does not influence its virulence. These results suggest that LaeA-regulated secondary metabolites are virulence factors in the genomic and phenotypic background of the major Pathogen A. fumigatus but are much less important in the background of the nonPathogen A. fischeri. Understanding the observed spectrum of Pathogenicity across closely related Pathogenic and nonPathogenic Aspergillus species will require detailed characterization of their biological, chemical, and genomic similarities and differences. IMPORTANCEAspergillus fumigatus is a major opportunistic fungal Pathogen of Humans, but most of its close relatives are nonPathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its close nonPathogenic relatives are similar or different with respect to virulence-associated traits. We investigated whether Aspergillus fischeri, a nonPathogenic close relative of A. fumigatus, can produce gliotoxin, a mycotoxin known to contribute to A. fumigatus virulence. We discovered that the nonPathogenic A. fischeri produces gliotoxin under the same conditions as those of the major Pathogen A. fumigatus. However, we also discovered that, in contrast to what has previously been observed in A. fumigatus, the loss of secondary metabolite production in A. fischeri does not alter its virulence. Our results are consistent with the “cards of virulence” model of opportunistic fungal disease, in which the ability to cause disease stems from the combination (“hand”) of virulence factors (“cards”) but not from individual factors per se.
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gliotoxin a known virulence factor in the major Human Pathogen aspergillus fumigatus is also biosynthesized by the non Pathogenic relative a fischeri
bioRxiv, 2019Co-Authors: Sonja L Knowles, Matthew E Mead, Lilian Pereira Silva, Huzefa A Raja, Jacob L Steenwyk, Antonis Rokas, Gustavo H Goldma, Nicholas H OberliesAbstract:ABSTRACT Aspergillus fumigatus is a major opportunistic Human Pathogen. Multiple traits contribute to A. fumigatus Pathogenicity, including its ability to produce specific secondary metabolites, such as gliotoxin. Gliotoxin is known to inhibit the host immune response, and genetic mutants that inactivate gliotoxin biosynthesis (or secondary metabolism in general) attenuate A. fumigatus virulence. The genome of A. fischeri, a very close non-Pathogenic relative of A. fumigatus, contains a biosynthetic gene cluster that exhibits high sequence similarity to the A. fumigatus gliotoxin cluster. However, A. fischeri is not known to produce gliotoxin. To gain further insight into the similarities and differences between the major Pathogen A. fumigatus and the non-Pathogen A. fischeri, we examined whether A. fischeri strain NRRL 181 biosynthesizes gliotoxin and whether its production, and of secondary metabolites more generally, influence its virulence profile. We found that A. fischeri biosynthesizes gliotoxin in the same conditions as A. fumigatus. However, whereas loss of laeA, a master regulator of secondary metabolite production, has been previously shown to reduce the virulence of A. fumigatus, we found that laeA loss (and loss of secondary metabolite production, including gliotoxin) in A. fischeri does not influence its virulence. These results suggest that gliotoxin and secondary metabolite production are virulence factors in the genomic and phenotypic background of the major Pathogen A. fumigatus but are much less important in the background of the non-Pathogen A. fischeri. We submit that understanding the observed spectrum of Pathogenicity across closely related Pathogenic and non-Pathogenic Aspergillus species will require detailed characterization of their biological, chemical, and genomic similarities and differences. IMPORTANCE Aspergillus fumigatus is a major opportunistic fungal Pathogen of Humans but most of its close relatives are non-Pathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its non-Pathogenic close relatives are similar or different with respect to virulence-associated traits. We investigated whether Aspergillus fischeri, a non-Pathogenic close relative of A. fumigatus, can produce gliotoxin, a mycotoxin known to contribute to A. fumigatus virulence. We discovered that the non-Pathogenic A. fischeri produces gliotoxin under the same conditions as the major Pathogen A. fumigatus. However, we also discovered that, in contrast to what has been previously observed in A. fumigatus, loss of secondary metabolite, including gliotoxin, production in A. fischeri does not alter its virulence. Our results are consistent with the “cards of virulence” model of opportunistic fungal disease, where the ability to cause disease stems from the combination (“hand”) of individual virulence factors (“cards”), but not from individual factors per se.
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an laea and brla dependent cellular network governs tissue specific secondary metabolism in the Human Pathogen aspergillus fumigatus
mSphere, 2018Co-Authors: Abigail L Lind, Fang Yun Lim, Alexandra A Soukup, Nancy P Keller, Antonis RokasAbstract:Biosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA > AbaA > WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of ΔbrlA, ΔabaA, and ΔwetA mutant and wild-type strains of the Human Pathogen Aspergillus fumigatus. We find that BrlA, in addition to regulating production of developmental SMs, regulates vegetative SMs and the SrbA-regulated hypoxia stress response in a concordant fashion to LaeA. We further show that the transcriptional and metabolic equivalence of the ΔbrlA and ΔlaeA mutations is mediated by an LaeA requirement preventing heterochromatic marks in the brlA promoter. These results provide a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this Pathogen. IMPORTANCE Filamentous fungi produce a spectacular variety of small molecules, commonly known as secondary or specialized metabolites (SMs), which are critical to their ecologies and lifestyles (e.g., penicillin, cyclosporine, and aflatoxin). Elucidation of the regulatory network that governs SM production is a major question of both fundamental and applied research relevance. To shed light on the relationship between regulation of development and regulation of secondary metabolism in filamentous fungi, we performed global transcriptomic and metabolomic analyses on mutant and wild-type strains of the Human Pathogen Aspergillus fumigatus under conditions previously shown to induce the production of both vegetative growth-specific and asexual development-specific SMs. We find that the gene brlA, previously known as a master regulator of asexual development, is also a master regulator of secondary metabolism and other cellular processes. We further show that brlA regulation of SM is mediated by laeA, one of the master regulators of SM, providing a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this Pathogen.
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a laea and brla dependent cellular network governs tissue specific secondary metabolism in the Human Pathogen aspergillus fumigatus
bioRxiv, 2017Co-Authors: Abigail L Lind, Fang Yun Lim, Alexandra A Soukup, Nancy P Keller, Antonis RokasAbstract:Biosynthesis of many ecologically important secondary metabolites (SMs) in filamentous fungi is controlled by several global transcriptional regulators, like the chromatin modifier LaeA, and tied to both development and vegetative growth. In Aspergillus molds, asexual development is regulated by the BrlA>AbaA>WetA transcriptional cascade. To elucidate BrlA pathway involvement in SM regulation, we examined the transcriptional and metabolic profiles of ΔbrlA, ΔabaA, ΔwetA and wild-type strains of the Human Pathogen Aspergillus fumigatus. We find that BrlA, in addition to regulating production of developmental SMs, regulates vegetative SMs and the SrbA-regulated hypoxia stress response in a concordant fashion to LaeA. We further show that the transcriptional and metabolic equivalence of ΔbrlA and ΔlaeA is mediated by a LaeA requirement preventing heterochromatic marks in the brlA promoter. The epistatic effect of LaeA to BrlA, coupled with the BrlA-dependent regulation of SM production in a tissue-specific manner, provides a framework for the cellular network regulating not only fungal SMs but diverse cellular processes linked to virulence of this Pathogen.
Eric W. Deutsch - One of the best experts on this subject based on the ideXlab platform.
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Visual proteomics of the Human Pathogen Leptospira interrogans.
Nature Methods, 2009Co-Authors: Martin Beck, Johan Malmström, Vinzenz Lange, M Alexander Schmidt, Eric W. DeutschAbstract:Systems biology conceptualizes biological systems as dynamic networks of interacting elements, whereby functionally important properties are thought to emerge from the structure of such networks. Owing to the ubiquitous role of complexes of interacting proteins in biological systems, their subunit composition and temporal and spatial arrangement within the cell are of particular interest. 'Visual proteomics' attempts to localize individual macromolecular complexes inside of intact cells by template matching reference structures into cryo-electron tomograms. Here we combined quantitative mass spectrometry and cryo-electron tomography to detect, count and localize specific protein complexes in the cytoplasm of the Human Pathogen Leptospira interrogans. We describe a scoring function for visual proteomics and assess its performance and accuracy under realistic conditions. We discuss current and general limitations of the approach, as well as expected improvements in the future.
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proteome wide cellular protein concentrations of the Human Pathogen leptospira interrogans
Nature, 2009Co-Authors: Johan Malmström, Martin Beck, Vinzenz Lange, Alexander Schmidt, Eric W. DeutschAbstract:Mass-spectrometry-based methods for relative proteome quantification have broadly affected life science research. However, important research directions, particularly those involving mathematical modelling and simulation of biological processes, also critically depend on absolutely quantitative data--that is, knowledge of the concentration of the expressed proteins as a function of cellular state. Until now, absolute protein concentration measurements of a considerable fraction of the proteome (73%) have only been derived from genetically altered Saccharomyces cerevisiae cells, a technique that is not directly portable from yeast to other species. Here we present a mass-spectrometry-based strategy to determine the absolute quantity, that is, the average number of protein copies per cell in a cell population, for a large fraction of the proteome in genetically unperturbed cells. Applying the technology to the Human Pathogen Leptospira interrogans, a spirochete responsible for leptospirosis, we generated an absolute protein abundance scale for 83% of the mass-spectrometry-detectable proteome, from cells at different states. Taking advantage of the unique cellular dimensions of L. interrogans, we used cryo-electron tomography morphological measurements to verify, at the single-cell level, the average absolute abundance values of selected proteins determined by mass spectrometry on a population of cells. Because the strategy is relatively fast and applicable to any cell type, we expect that it will become a cornerstone of quantitative biology and systems biology.
