Fishing for phages in metagenomes: what do we catch, what do we miss?
TL;DR: The continued success of metagenomics hinges on the combination of the most powerful computational methods for phage genome assembly and analysis including harnessing CRISPR spacers for the discovery of novel phages and host assignment as discussed by the authors.
About: This article is published in Current Opinion in Virology.The article was published on 2021-08-01. It has received 6 citations till now. The article focuses on the topics: RNA Phages & Metagenomics.
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TL;DR: In this article , the authors discuss phage uptake by mammalian cells, focusing on mechanisms and pathways involved, and identify this process as a type of endocytosis within a larger repertoire of end-ocytic pathways, which have all been included in the scope of this review.
7 citations
TL;DR: This study, along with the two previous bee virome studies, shows that the bee gut bacteriophage community is simple compared to that of many animals, consisting of several hundred types of bacter iophages that primarily infect four of the dominant bacterial phylotypes in the bee Gut.
Abstract: Viruses that infect bacteria (bacteriophages) are abundant in the microbial communities that live on and in plants and animals. However, our knowledge of the structure, dynamics, and function of these viral communities lags far behind our knowledge of their bacterial hosts. ABSTRACT The microbial communities in animal digestive systems are critical for host development and health. They stimulate the immune system during development, synthesize important chemical compounds like hormones, aid in digestion, competitively exclude pathogens, etc. Compared to the bacterial and fungal components of the microbiome, we know little about the temporal and spatial dynamics of bacteriophage communities in animal digestive systems. Recently, the bacteriophages of the honey bee gut were characterized in two European bee populations. Most of the bacteriophages described in these two reports were novel, harbored many metabolic genes in their genomes, and had a community structure that suggests coevolution with their bacterial hosts. To describe the conservation of bacteriophages in bees and begin to understand their role in the bee microbiome, we sequenced the virome of Apis mellifera from Austin, TX, and compared bacteriophage compositions among three locations around the world. We found that most bacteriophages from Austin are novel, sharing no sequence similarity with anything in public repositories. However, many bacteriophages are shared among the three bee viromes, indicating specialization of bacteriophages in the bee gut. Our study, along with the two previous bee virome studies, shows that the bee gut bacteriophage community is simple compared to that of many animals, consisting of several hundred types of bacteriophages that primarily infect four of the dominant bacterial phylotypes in the bee gut. IMPORTANCE Viruses that infect bacteria (bacteriophages) are abundant in the microbial communities that live on and in plants and animals. However, our knowledge of the structure, dynamics, and function of these viral communities lags far behind our knowledge of their bacterial hosts. We sequenced the first bacteriophage community of honey bees from the United States and compared the U.S. honey bee bacteriophage community to those of samples from Europe. Our work is an important characterization of an economically critical insect species and shows how bacteriophage communities can contain highly conserved individuals and be highly variable in composition across a wide geographic range.
2 citations
TL;DR: The bacteriophages in animal microbiomes are harder to characterize than the bacterial or fungal components of the microbiome and thus, we know comparatively little about the temporal and spatial dynamics of bacterial communities in animal digestive systems as mentioned in this paper.
Abstract: The microbial communities in animal digestive systems are critical to host development and health. These assemblages of primarily viruses, bacteria, and fungi stimulate the immune system during development, synthesize important chemical compounds like hormones, aid in digestion, competitively exclude pathogens, etc. The bacteriophages in animal microbiomes are harder to characterize than the bacterial or fungal components of the microbiome and thus we know comparatively little about the temporal and spatial dynamics of bacteriophage communities in animal digestive systems. Recently, the bacteriophages of the honeybee gut were characterized in two European bee populations. Most of the bacteriophages described in these two reports were novel, encoded many metabolic genes in their genomes, and had a community structure that suggests coevolution with their bacterial hosts. To describe the conservation of bacteriophages in bees and begin to understand their role in the bee microbiome, we sequenced the virome of Apis mellifera from Austin, Texas and compared bacteriophage composition between three locations around the world. We found that the majority of bacteriophages from Austin are novel, sharing no sequence similarity to anything in public repositories. However, many bacteriophages are shared among the three bee viromes, indicating specialization of bacteriophages in the bee gut. Our study along with the two previous bee virome studies shows that the bee gut bacteriophage community is simple compared to that of many animals, consisting of several hundred types of bacteriophages that primarily infect four of the dominant bacterial phylotypes in the bee gut.
1 citations
TL;DR: In this paper , the authors integrated multi-omics of supragingival biofilm (dental plaque) from 416 preschool-age children (208 males and 208 females) in a discovery-validation pipeline to identify disease-relevant inter-species interactions.
Abstract: Streptococcus mutans has been implicated as the primary pathogen in childhood caries (tooth decay). While the role of polymicrobial communities is appreciated, it remains unclear whether other microorganisms are active contributors or interact with pathogens. Here, we integrate multi-omics of supragingival biofilm (dental plaque) from 416 preschool-age children (208 males and 208 females) in a discovery-validation pipeline to identify disease-relevant inter-species interactions. Sixteen taxa associate with childhood caries in metagenomics-metatranscriptomics analyses. Using multiscale/computational imaging and virulence assays, we examine biofilm formation dynamics, spatial arrangement, and metabolic activity of Selenomonas sputigena, Prevotella salivae and Leptotrichia wadei, either individually or with S. mutans. We show that S. sputigena, a flagellated anaerobe with previously unknown role in supragingival biofilm, becomes trapped in streptococcal exoglucans, loses motility but actively proliferates to build a honeycomb-like multicellular-superstructure encapsulating S. mutans, enhancing acidogenesis. Rodent model experiments reveal an unrecognized ability of S. sputigena to colonize supragingival tooth surfaces. While incapable of causing caries on its own, when co-infected with S. mutans, S. sputigena causes extensive tooth enamel lesions and exacerbates disease severity in vivo. In summary, we discover a pathobiont cooperating with a known pathogen to build a unique spatial structure and heighten biofilm virulence in a prevalent human disease.
1 citations
TL;DR: This work focuses on a subset of viruses that is highly abundant in the gut, remains largely uncharacterized, and allows confident complete genome identification – phages that belong to the class Caudoviricetes and possess genome terminal repeats.
Abstract: The human gut harbors numerous viruses infecting the human host, microbes and other inhabitants of the gastrointestinal tract. Most of these viruses remain undiscovered, and their influence on human health is unknown. Here we characterize viral genomes in gut metagenomic data from 1,950 individuals from four population and patient cohorts. We focus on a subset of viruses that is highly abundant in the gut, remains largely uncharacterized, and allows confident complete genome identification – phages that belong to the class Caudoviricetes and possess genome terminal repeats. We detect 1,899 species-level units belonging to this subset, 19% of which do not have complete representative genomes in major public gut virome databases. These units display diverse genomic features, are predicted to infect a wide range of microbial hosts, and on average account for < 1% of metagenomic reads. Analysis of longitudinal data from 338 individuals shows that the composition of this fraction of the virome remained relatively stable over a period of 4 years. We also demonstrate that 54 species-level units are highly prevalent (detected in > 5% of individuals in a cohort). Finally, we find 34 associations between highly prevalent phages and human phenotypes, 24 of which can be explained by the relative abundance of potential hosts.
References
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TL;DR: MetaSPAdes as mentioned in this paper addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes.
Abstract: While metagenomics has emerged as a technology of choice for analyzing bacterial populations, the assembly of metagenomic data remains challenging, thus stifling biological discoveries. Moreover, recent studies revealed that complex bacterial populations may be composed from dozens of related strains, thus further amplifying the challenge of metagenomic assembly. metaSPAdes addresses various challenges of metagenomic assembly by capitalizing on computational ideas that proved to be useful in assemblies of single cells and highly polymorphic diploid genomes. We benchmark metaSPAdes against other state-of-the-art metagenome assemblers and demonstrate that it results in high-quality assemblies across diverse data sets.
2,295 citations
National Institutes of Health1, Delft University of Technology2, Humboldt University of Berlin3, DuPont4, Laval University5, University of Alicante6, University of Copenhagen7, Vilnius University8, University of Georgia9, University of St Andrews10, University of Toronto11, Bangor University12, University of Freiburg13, Wageningen University and Research Centre14, North Carolina State University15
TL;DR: An updated evolutionary classification of CRISPR–Cas systems and cas genes is provided, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015, which includes 2 classes, 6 types and 33 subtypes.
Abstract: The number and diversity of known CRISPR-Cas systems have substantially increased in recent years. Here, we provide an updated evolutionary classification of CRISPR-Cas systems and cas genes, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015. The new classification includes 2 classes, 6 types and 33 subtypes, compared with 5 types and 16 subtypes in 2015. A key development is the ongoing discovery of multiple, novel class 2 CRISPR-Cas systems, which now include 3 types and 17 subtypes. A second major novelty is the discovery of numerous derived CRISPR-Cas variants, often associated with mobile genetic elements that lack the nucleases required for interference. Some of these variants are involved in RNA-guided transposition, whereas others are predicted to perform functions distinct from adaptive immunity that remain to be characterized experimentally. The third highlight is the discovery of numerous families of ancillary CRISPR-linked genes, often implicated in signal transduction. Together, these findings substantially clarify the functional diversity and evolutionary history of CRISPR-Cas.
1,153 citations
TL;DR: DNA and predicted protein sequence similarities, implying homology, are reported, among genes of double-stranded DNA (dsDNA) bacteriophages and prophages spanning a broad phylogenetic range of host bacteria, suggesting common ancestry among these phage genes.
Abstract: We report DNA and predicted protein sequence similarities, implying homology, among genes of double-stranded DNA (dsDNA) bacteriophages and prophages spanning a broad phylogenetic range of host bacteria. The sequence matches reported here establish genetic connections, not always direct, among the lambdoid phages of Escherichia coli, phage phiC31 of Streptomyces, phages of Mycobacterium, a previously unrecognized cryptic prophage, phiflu, in the Haemophilus influenzae genome, and two small prophage-like elements, phiRv1 and phiRv2, in the genome of Mycobacterium tuberculosis. The results imply that these phage genes, and very possibly all of the dsDNA tailed phages, share common ancestry. We propose a model for the genetic structure and dynamics of the global phage population in which all dsDNA phage genomes are mosaics with access, by horizontal exchange, to a large common genetic pool but in which access to the gene pool is not uniform for all phage.
929 citations
TL;DR: Diversity of the viral communities was extremely high, and the results showed that it would be possible to sequence the entire genome of an uncultured marine viral community.
Abstract: Viruses are the most common biological entities in the oceans by an order of magnitude. However, very little is known about their diversity. Here we report a genomic analysis of two uncultured marine viral communities. Over 65% of the sequences were not significantly similar to previously reported sequences, suggesting that much of the diversity is previously uncharacterized. The most common significant hits among the known sequences were to viruses. The viral hits included sequences from all of the major families of dsDNA tailed phages, as well as some algal viruses. Several independent mathematical models based on the observed number of contigs predicted that the most abundant viral genome comprised 2–3% of the total population in both communities, which was estimated to contain between 374 and 7,114 viral types. Overall, diversity of the viral communities was extremely high. The results also showed that it would be possible to sequence the entire genome of an uncultured marine viral community.
916 citations
TL;DR: The method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection suggests that the methods described here for the production of bacteriophile therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriaphages for MDR bacterial infections are warranted.
Abstract: Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
718 citations