scholarly journals Thousands of previously unknown phages discovered in whole-community human gut metagenomes

2021 ◽  
Author(s):  
Sean Benler ◽  
Natalya Yutin ◽  
Dmitry Antipov ◽  
Mikhail Raykov ◽  
Sergey Shmakov ◽  
...  
Keyword(s):  
Target Genes ◽  
Functional Characterization ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
Host Interactions ◽  
Family Protein ◽  
Host Cell Wall ◽  
Cellular Tolerance

Abstract Background: Double-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut virome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut.Results: A search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3,738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, “Flandersviridae” and “Quimbyviridae”, include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides and Prevotella. The third proposed family, “Gratiaviridae”, consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some “Quimbyviridae” phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several “Flandersviridae” phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The “Gratiaviridae” phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species.Conclusions: Analysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.

scholarly journals Thousands of previously unknown phages discovered in whole-community human gut metagenomes

2020 ◽  
Author(s):  
Sean Benler ◽  
Natalya Yutin ◽  
Dmitry Antipov ◽  
Mikhail Raykov ◽  
Sergey Shmakov ◽  
...  
Keyword(s):  
Target Genes ◽  
Functional Characterization ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
Host Interactions ◽  
Family Protein ◽  
Host Cell Wall ◽  
Cellular Tolerance

AbstractBackgroundDouble-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut phageome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut.ResultsA search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3,738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, “Flandersviridae” and “Quimbyviridae”, include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides and Prevotella. The third proposed family, “Gratiaviridae”, consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some “Quimbyviridae” phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several “Flandersviridae” phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The “Gratiaviridae” phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species.ConclusionsAnalysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.

scholarly journals Thousands of previously unknown phages discovered in whole-community human gut metagenomes

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sean Benler ◽  
Natalya Yutin ◽  
Dmitry Antipov ◽  
Mikhail Rayko ◽  
Sergey Shmakov ◽  
...  
Keyword(s):  
Target Genes ◽  
Functional Characterization ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
Host Interactions ◽  
Family Protein ◽  
Host Cell Wall ◽  
Cellular Tolerance

Abstract Background Double-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut virome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut. Results A search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, “Flandersviridae” and “Quimbyviridae”, include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides, and Prevotella. The third proposed family, “Gratiaviridae,” consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae, and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some “Quimbyviridae” phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several “Flandersviridae” phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The “Gratiaviridae” phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species. Conclusions Analysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse, and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.

scholarly journals Thousands of Previously Unknown Phages Discovered in Whole-community Human Gut Metagenomes

2020 ◽  
Author(s):  
Sean Benler ◽  
Natalya Yutin ◽  
Dmitry Antipov ◽  
Mikhail Raykov ◽  
Sergey Shmakov ◽  
...  
Keyword(s):  
Target Genes ◽  
Functional Characterization ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
Host Interactions ◽  
Family Protein ◽  
Host Cell Wall ◽  
Cellular Tolerance

Abstract Background: Double-stranded DNA bacteriophages (dsDNA phages) play pivotal roles in structuring human gut microbiomes; yet, the gut phageome is far from being fully characterized, and additional groups of phages, including highly abundant ones, continue to be discovered by metagenome mining. A multilevel framework for taxonomic classification of viruses was recently adopted, facilitating the classification of phages into evolutionary informative taxonomic units based on hallmark genes. Together with advanced approaches for sequence assembly and powerful methods of sequence analysis, this revised framework offers the opportunity to discover and classify unknown phage taxa in the human gut.Results:A search of human gut metagenomes for circular contigs encoding phage hallmark genes resulted in the identification of 3,738 apparently complete phage genomes that represent 451 putative genera. Several of these phage genera are only distantly related to previously identified phages and are likely to found new families. Two of the candidate families, “Flandersviridae” and “Quimbyviridae”, include some of the most common and abundant members of the human gut virome that infect Bacteroides, Parabacteroides and Prevotella. The third proposed family, “Gratiaviridae”, consists of less abundant phages that are distantly related to the families Autographiviridae, Drexlerviridae and Chaseviridae. Analysis of CRISPR spacers indicates that phages of all three putative families infect bacteria of the phylum Bacteroidetes. Comparative genomic analysis of the three candidate phage families revealed features without precedent in phage genomes. Some “Quimbyviridae” phages possess Diversity-Generating Retroelements (DGRs) that generate hypervariable target genes nested within defense-related genes, whereas the previously known targets of phage-encoded DGRs are structural genes. Several “Flandersviridae” phages encode enzymes of the isoprenoid pathway, a lipid biosynthesis pathway that so far has not been known to be manipulated by phages. The “Gratiaviridae” phages encode a HipA-family protein kinase and glycosyltransferase, suggesting these phages modify the host cell wall, preventing superinfection by other phages. Hundreds of phages in these three and other families are shown to encode catalases and iron-sequestering enzymes that can be predicted to enhance cellular tolerance to reactive oxygen species.Conclusions:Analysis of phage genomes identified in whole-community human gut metagenomes resulted in the delineation of at least three new candidate families of Caudovirales and revealed diverse putative mechanisms underlying phage-host interactions in the human gut. Addition of these phylogenetically classified, diverse and distinct phages to public databases will facilitate taxonomic decomposition and functional characterization of human gut viromes.

scholarly journals Diversity, evolution, and classification of virophages uncovered through global metagenomics

Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
David Paez-Espino ◽  
Jinglie Zhou ◽  
Simon Roux ◽  
Stephen Nayfach ◽  
Georgios A. Pavlopoulos ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
High Quality ◽  
Double Stranded Dna ◽  
Terrestrial Subsurface ◽  
Public Collection ◽  
Reference Genomes ◽  
Core Genes

Abstract Background Virophages are small viruses with double-stranded DNA genomes that replicate along with giant viruses and co-infect eukaryotic cells. Due to the paucity of virophage reference genomes, a collective understanding of the global virophage diversity, distribution, and evolution is lacking. Results Here we screened a public collection of over 14,000 metagenomes using the virophage-specific major capsid protein (MCP) as “bait.” We identified 44,221 assembled virophage sequences, of which 328 represent high-quality (complete or near-complete) genomes from diverse habitats including the human gut, plant rhizosphere, and terrestrial subsurface. Comparative genomic analysis confirmed the presence of four core genes in a conserved block. We used these genes to establish a revised virophage classification including 27 clades with consistent genome length, gene content, and habitat distribution. Moreover, for eight high-quality virophage genomes, we computationally predicted putative eukaryotic virus hosts. Conclusion Overall, our approach has increased the number of known virophage genomes by 10-fold and revealed patterns of genome evolution and global virophage distribution. We anticipate that the expanded diversity presented here will provide the backbone for further virophage studies.

scholarly journals Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2

2020 ◽  
Author(s):  
Matteo Chiara ◽  
David S. Horner ◽  
Carmela Gissi ◽  
Graziano Pesole
Keyword(s):  
Classification System ◽  
Functional Characterization ◽  
Temporal Distribution ◽  
Genomic Analysis ◽  
Molecular Data ◽  
Comparative Genomic ◽  
Evolutionary Processes ◽  
Systematic Classification ◽  
Spatio Temporal

AbstractEffective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.

scholarly journals Whole-Genome Sequences and Classification of Streptococcus agalactiae Strains Isolated from Laboratory-Reared Long-Evans Rats (Rattus norvegicus)

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
C. Bodi Winn ◽  
J. Dzink-Fox ◽  
Y. Feng ◽  
Z. Shen ◽  
V. Bakthavatchalu ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Genomic Analysis ◽  
Opportunistic Pathogen ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
Long Evans ◽  
Fatal Septicemia

ABSTRACT In collaboration with the CDC’s Streptococcus Laboratory, we report here the whole-genome sequences of seven Streptococcus agalactiae bacteria isolated from laboratory-reared Long-Evans rats. Four of the S. agalactiae isolates were associated with morbidity accompanied by endocarditis, metritis, and fatal septicemia, providing an opportunity for comparative genomic analysis of this opportunistic pathogen.

scholarly journals Analysis of metagenome-assembled viral genomes from the human gut reveals diverse putative CrAss-like phages with unique genomic features

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Natalya Yutin ◽  
Sean Benler ◽  
Sergei A. Shmakov ◽  
Yuri I. Wolf ◽  
Igor Tolstoy ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Comparative Genomic ◽  
Human Gut ◽  
Genomic Features ◽  
Viral Genomes ◽  
Founding Member ◽  
Phage Dna ◽  
Conserved Genes ◽  
Phage Genomics ◽  
Self Splicing

AbstractCrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.

scholarly journals Complete Genome Sequencing and Comparative Genomics of Three Potential Probiotic Strains, Lacticaseibacillus casei FBL6, Lacticaseibacillus chiayiensis FBL7, and Lacticaseibacillus zeae FBL8

2022 ◽  
Vol 12 ◽  
Author(s):  
Eiseul Kim ◽  
Seung-Min Yang ◽  
Dayoung Kim ◽  
Hae-Yeong Kim
Keyword(s):  
Complete Genome ◽  
Functional Characterization ◽  
Genomic Analysis ◽  
Raw Milk ◽  
Phenotypic Characterization ◽  
Comparative Genomic ◽  
Probiotic Properties ◽  
Bacterial Strains ◽  
Physiological Control ◽  
Wide Range

Lacticaseibacillus casei, Lacticaseibacillus chiayiensis, and Lacticaseibacillus zeae are very closely related Lacticaseibacillus species. L. casei has long been proposed as a probiotic, whereas studies on functional characterization for L. chiayiensis and L. zeae are some compared to L. casei. In this study, L. casei FBL6, L. chiayiensis FBL7, and L. zeae FBL8 were isolated from raw milk, and their probiotic properties were investigated. Genomic analysis demonstrated the role of L. chiayiensis and L. zeae as probiotic candidates. The three strains were tolerant to acid and bile salt, with inhibitory action against pathogenic bacterial strains and capacity of antioxidants. Complete genome sequences of the three strains were analyzed to highlight the probiotic properties at the genetic level, which results in the discovery of genes corresponding to phenotypic characterization. Moreover, genes known to confer probiotic characteristics were identified, including genes related to biosynthesis, defense machinery, adhesion, and stress adaptation. The comparative genomic analysis with other available genomes revealed 256, 214, and 32 unique genes for FBL6, FBL7, and FBL8, respectively. These genomes contained individual genes encoding proteins that are putatively involved in carbohydrate transport and metabolism, prokaryotic immune system for antiviral defense, and physiological control processes. In particular, L. casei FBL6 had a bacteriocin gene cluster that was not present in other genomes of L. casei, resulting in this strain may exhibit a wide range of antimicrobial activity compared to other L. casei strains. Our data can help us understand the probiotic functionalities of the three strains and suggest that L. chiayiensis and L. zeae species, which are closely related to L. casei, can also be considered as novel potential probiotic candidate strains.

scholarly journals Reverse vaccinology and subtractive genomics reveal new therapeutic targets against Mycoplasma pneumoniae : a causative agent of pneumonia

2019 ◽  
Vol 6 (7) ◽  
pp. 190907 ◽  
Author(s):  
Thaís Cristina Vilela Rodrigues ◽  
Arun Kumar Jaiswal ◽  
Alissa de Sarom ◽  
Letícia de Castro Oliveira ◽  
Carlo José Freire Oliveira ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Drug Targets ◽  
Genomic Analysis ◽  
Community Acquired Pneumonia ◽  
Reverse Vaccinology ◽  
Comparative Genomic ◽  
Host Interactions ◽  
Subtractive Genomics ◽  
Cytoplasmic Proteins

Pneumonia is an infectious disease caused by bacteria, viruses or fungi that results in millions of deaths globally. Despite the existence of prophylactic methods against some of the major pathogens of the disease, there is no efficient prophylaxis against atypical agents such as Mycoplasma pneumoniae , a bacterium associated with cases of community-acquired pneumonia. Because of the morphological peculiarity of M. pneumoniae , which leads to an increased resistance to antibiotics, studies that prospectively investigate the development of vaccines and drug targets appear to be one of the best ways forward. Hence, in this paper, bioinformatics tools were used for vaccine and pharmacological prediction. We conducted comparative genomic analysis on the genomes of 88 M. pneumoniae strains, as opposed to a reverse vaccinology analysis, in relation to the capacity of M. pneumoniae proteins to bind to the major histocompatibility complex, revealing seven targets with immunogenic potential. Predictive cytoplasmic proteins were tested as potential drug targets by studying their structures in relation to other proteins, metabolic pathways and molecular anchorage, which identified five possible drug targets. These findings are a valuable addition to the development of vaccines and the selection of new in vivo drug targets that may contribute to further elucidating the molecular basis of M. pneumoniae –host interactions.

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