Suresh Poudel

Bio: Suresh Poudel is an academic researcher from Oak Ridge National Laboratory. The author has contributed to research in topics: Proteome & Metagenomics. The author has an hindex of 8, co-authored 18 publications receiving 625 citations. Previous affiliations of Suresh Poudel include University of Tennessee & St. Jude Children's Research Hospital.

Insights from 20 years of bacterial genome sequencing

Abstract: Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date, there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.

Outer membrane vesicles catabolize lignin-derived aromatic compounds in Pseudomonas putida KT2440

Abstract: Lignin is an abundant and recalcitrant component of plant cell walls. While lignin degradation in nature is typically attributed to fungi, growing evidence suggests that bacteria also catabolize this complex biopolymer. However, the spatiotemporal mechanisms for lignin catabolism remain unclear. Improved understanding of this biological process would aid in our collective knowledge of both carbon cycling and microbial strategies to valorize lignin to value-added compounds. Here, we examine lignin modifications and the exoproteome of three aromatic–catabolic bacteria: Pseudomonas putida KT2440, Rhodoccocus jostii RHA1, and Amycolatopsis sp. ATCC 39116. P. putida cultivation in lignin-rich media is characterized by an abundant exoproteome that is dynamically and selectively packaged into outer membrane vesicles (OMVs). Interestingly, many enzymes known to exhibit activity toward lignin-derived aromatic compounds are enriched in OMVs from early to late stationary phase, corresponding to the shift from bioavailable carbon to oligomeric lignin as a carbon source. In vivo and in vitro experiments demonstrate that enzymes contained in the OMVs are active and catabolize aromatic compounds. Taken together, this work supports OMV-mediated catabolism of lignin-derived aromatic compounds as an extracellular strategy for nutrient acquisition by soil bacteria and suggests that OMVs could potentially be useful tools for synthetic biology and biotechnological applications.

Proteomic landscape of Alzheimer's Disease: novel insights into pathogenesis and biomarker discovery.

Abstract: Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies. Supplementary Information The online version contains supplementary material available at 10.1186/s13024-021-00474-z.

Functional Analysis of the Glucan Degradation Locus in Caldicellulosiruptor bescii Reveals Essential Roles of Component Glycoside Hydrolases in Plant Biomass Deconstruction.

Abstract: The ability to hydrolyze microcrystalline cellulose is an uncommon feature in the microbial world, but it can be exploited for conversion of lignocellulosic feedstocks into biobased fuels and chemicals. Understanding the physiological and biochemical mechanisms by which microorganisms deconstruct cellulosic material is key to achieving this objective. The glucan degradation locus (GDL) in the genomes of extremely thermophilic Caldicellulosiruptor species encodes polysaccharide lyases (PLs), unique cellulose binding proteins (tāpirins), and putative posttranslational modifying enzymes, in addition to multidomain, multifunctional glycoside hydrolases (GHs), thereby representing an alternative paradigm for plant biomass degradation compared to fungal or cellulosomal systems. To examine the individual and collective in vivo roles of the glycolytic enzymes, the six GH genes in the GDL of Caldicellulosiruptor bescii were systematically deleted, and the extents to which the resulting mutant strains could solubilize microcrystalline cellulose (Avicel) and plant biomass (switchgrass or poplar) were examined. Three of the GDL enzymes, Athe_1867 (CelA) (GH9-CBM3-CBM3-CBM3-GH48), Athe_1859 (GH5-CBM3-CBM3-GH44), and Athe_1857 (GH10-CBM3-CBM3-GH48), acted synergistically in vivo and accounted for 92% of naked microcrystalline cellulose (Avicel) degradation. However, the relative importance of the GDL GHs varied for the plant biomass substrates tested. Furthermore, mixed cultures of mutant strains showed that switchgrass solubilization depended on the secretome-bound enzymes collectively produced by the culture, not on the specific strain from which they came. These results demonstrate that certain GDL GHs are primarily responsible for the degradation of microcrystalline cellulose-containing substrates by C. bescii and provide new insights into the workings of a novel microbial mechanism for lignocellulose utilization.IMPORTANCE The efficient and extensive degradation of complex polysaccharides in lignocellulosic biomass, particularly microcrystalline cellulose, remains a major barrier to its use as a renewable feedstock for the production of fuels and chemicals. Extremely thermophilic bacteria from the genus Caldicellulosiruptor rapidly degrade plant biomass to fermentable sugars at temperatures of 70 to 78°C, although the specific mechanism by which this occurs is not clear. Previous comparative genomic studies identified a genomic locus found only in certain Caldicellulosiruptor species that was hypothesized to be mainly responsible for microcrystalline cellulose degradation. By systematically deleting genes in this locus in Caldicellulosiruptor bescii, the nuanced, substrate-specific in vivo roles of glycolytic enzymes in deconstructing crystalline cellulose and plant biomasses could be discerned. The results here point to synergism of three multidomain cellulases in C. bescii, working in conjunction with the aggregate secreted enzyme inventory, as the key to the plant biomass degradation ability of this extreme thermophile.

A global atlas of the dominant bacteria found in soil

Abstract: The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a “most wanted” list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.

TYGS is an automated high-throughput platform for state-of-the-art genome-based taxonomy

Abstract: Microbial taxonomy is increasingly influenced by genome-based computational methods. Yet such analyses can be complex and require expert knowledge. Here we introduce TYGS, the Type (Strain) Genome Server, a user-friendly high-throughput web server for genome-based prokaryote taxonomy, connected to a large, continuously growing database of genomic, taxonomic and nomenclatural information. It infers genome-scale phylogenies and state-of-the-art estimates for species and subspecies boundaries from user-defined and automatically determined closest type genome sequences. TYGS also provides comprehensive access to nomenclature, synonymy and associated taxonomic literature. Clinically important examples demonstrate how TYGS can yield new insights into microbial classification, such as evidence for a species-level separation of previously proposed subspecies of Salmonella enterica. TYGS is an integrated approach for the classification of microbes that unlocks novel scientific approaches to microbiologists worldwide and is particularly helpful for the rapidly expanding field of genome-based taxonomic descriptions of new genera, species or subspecies.

An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography

Abstract: We present the Metagenomic Intra-species Diversity Analysis System (MIDAS), which is an integrated computational pipeline for quantifying bacterial species abundance and strain-level genomic variation, including gene content and single-nucleotide polymorphisms (SNPs), from shotgun metagenomes. Our method leverages a database of more than 30,000 bacterial reference genomes that we clustered into species groups. These cover the majority of abundant species in the human microbiome but only a small proportion of microbes in other environments, including soil and seawater. We applied MIDAS to stool metagenomes from 98 Swedish mothers and their infants over one year and used rare SNPs to track strains between hosts. Using this approach, we found that although species compositions of mothers and infants converged over time, strain-level similarity diverged. Specifically, early colonizing bacteria were often transmitted from an infant's mother, while late colonizing bacteria were often transmitted from other sources in the environment and were enriched for spore-formation genes. We also applied MIDAS to 198 globally distributed marine metagenomes and used gene content to show that many prevalent bacterial species have population structure that correlates with geographic location. Strain-level genetic variants present in metagenomes clearly reveal extensive structure and dynamics that are obscured when data are analyzed at a coarser taxonomic resolution.

Genome Project Standards in a New Era of Sequencing

Abstract: A Joint Announcement on Genome Sequence Standards Genome project standards in a new era of sequencing P. S. G. Chain 1,2,3,4,22,* , D. V. Grafham 5,* , R. S. Fulton 6 , M. G. FitzGerald 7 , J. Hostetler 8 , D. Muzny 9 , J. C. Detter 1,10 , J. Ali 11 , B.Birren 7 , D. C. Bruce 1, 10 , C. Buhay 9 , J. R. Cole 3,4 , Y. Ding 9 , S. Dugan 9 , D. Field 12 , G. M. Garrity 3,4 , R. Gibbs 9 , T. Graves 6 , C. S. Han 1, 10 , S. H. Harrison 3 , S. Highlander 9 , P. Hugenholtz 1 , H. M. Khouri 13 , C. D. Kodira 7,23 , E. Kolker 14,15 , N. C. Kyrpides 1 , D. Lang 1,2 , A. Lapidus 1 , S. A. Malfatti 1,2 , V. Markowitz 16 , T. Metha 7 , K. E. Nelson 8 , J. Parkhill 5 , S. Pitluck 1 , X. Qin 9 , T. D. Read 17 , J. Schmutz 18 , S. Sozhamannan 19 , R. Strausberg 8 , G. Sutton 8 , N. R. Thomson 5 , J. M. Tiedje 3,4 , G. Weinstock 6 , A. Wollam 6 , and the entire GSC 20 and HMP Jumpstart 21 consortia. U.S. Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA Center for Microbial Ecology, Michigan State University, East Lansing, Michigan 48824, USA The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom The Genome Center, Washington University School of Medicine, St Louis, Missouri 63108, USA The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02141, USA J. Craig Venter Institute, Rockville, Maryland 20850, USA Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Natural Environmental Research Council Centre for Ecology and Hydrology, Oxford, Oxfordshire OX1 3SR, UK National Center for Biotechnology Information, National Library of Medicine, Rockville, Maryland 20850, USA Seattle Children’s Hospital and Research Institute, Seattle, Washington 98101, USA Biomedical & Health Informatics Division, MEBI, University of Washington School of Medicine, Seattle, Washington 98195, USA Biological Data Management and Technology Center, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA Emory GRA Genomics Core, Emory University School of Medicine, Atlanta, Georgia 30322, USA HudsonAlpha Genome Sequencing Center, HudsonAlpha Institute, Huntsville, Alabama 35806, USA Biological Defense Research Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910, USA Genomic Standards Consortium Human Microbiome Project Jumpstart Consortium Current address: Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA Current address: 454 Life Sciences, Branford, Connecticut 06405, USA *Address correspondence to Patrick Chain (pchain@lanl.gov) and Darren Grafham (dg1@sanger.ac.uk)