RESUMO
Sickle cell disease (SCD) is an inherited disorder resulting from a ß-globin gene mutation, and SCD patients experience erythrocyte sickling, vaso-occlusive episodes (VOE), and progressive organ damage. Chronic hemolysis, inflammation, and repeated red blood cell transfusions in SCD can disrupt iron homeostasis. Patients who receive multiple blood transfusions develop iron overload, and another subpopulation of SCD patients manifest iron deficiency. To elucidate connections between dietary iron, the microbiome, and SCD pathogenesis, we treated SCD mice with an iron-restricted diet (IRD). IRD treatment reduced iron availability and hemolysis, decreased acute VOE, and ameliorated chronic organ damage in SCD mice. Our results extend previous studies indicating that the gut microbiota regulate disease in SCD mice. IRD alters microbiota load and improves gut integrity, together preventing crosstalk between the gut microbiome and inflammatory factors such as aged neutrophils, dampening VOE, and organ damage. These findings provide strong evidence for the therapeutic potential of manipulating iron homeostasis and the gut microbiome to ameliorate SCD pathophysiology. Many treatments, which are under development, focus on lowering the systemic iron concentration to relieve disease complications, and our data suggest that iron-induced changes in microbiota load and gut integrity are related- and novel-therapeutic targets.
Assuntos
Anemia Falciforme , Doenças Vasculares , Camundongos , Animais , Ferro da Dieta , Ferro , Hemólise , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Doenças Vasculares/etiologia , Doenças Vasculares/prevenção & controleRESUMO
In the past decade of microbiome research, we have learned about numerous adverse interactions between the microbiome and medical interventions such as drugs, radiation, and surgery. What if we could alter our microbiomes to prevent these events? In this review, we discuss potential routes to mitigate microbiome adverse events, including applications from the emerging field of microbiome engineering. We highlight cases where the microbiome acts directly on a treatment, such as via differential drug metabolism, and cases where a treatment directly harms the microbiome, such as in radiation therapy. Understanding and preventing microbiome adverse events is a difficult challenge that will require a data-driven approach involving causal statistics, multiomics techniques, and a personalized means of mitigating adverse events. We propose research considerations to encourage productive work in preventing microbiome adverse events, and we highlight the many challenges and opportunities that await.
Assuntos
Microbioma Gastrointestinal , Microbiota , Preparações Farmacêuticas , HumanosRESUMO
The most abundant viruses on Earth are thought to be double-stranded DNA (dsDNA) viruses that infect bacteria. However, tailed bacterial dsDNA viruses (Caudovirales), which dominate sequence and culture collections, are not representative of the environmental diversity of viruses. In fact, non-tailed viruses often dominate ocean samples numerically, raising the fundamental question of the nature of these viruses. Here we characterize a group of marine dsDNA non-tailed viruses with short 10-kb genomes isolated during a study that quantified the diversity of viruses infecting Vibrionaceae bacteria. These viruses, which we propose to name the Autolykiviridae, represent a novel family within the ancient lineage of double jelly roll (DJR) capsid viruses. Ecologically, members of the Autolykiviridae have a broad host range, killing on average 34 hosts in four Vibrio species, in contrast to tailed viruses which kill on average only two hosts in one species. Biochemical and physical characterization of autolykiviruses reveals multiple virion features that cause systematic loss of DJR viruses in sequencing and culture-based studies, and we describe simple procedural adjustments to recover them. We identify DJR viruses in the genomes of diverse major bacterial and archaeal phyla, and in marine water column and sediment metagenomes, and find that their diversity greatly exceeds the diversity that is currently captured by the three recognized families of such viruses. Overall, these data suggest that viruses of the non-tailed dsDNA DJR lineage are important but often overlooked predators of bacteria and archaea that impose fundamentally different predation and gene transfer regimes on microbial systems than on tailed viruses, which form the basis of all environmental models of bacteria-virus interactions.
Assuntos
Organismos Aquáticos/virologia , Bactérias/virologia , Vírus de DNA/classificação , Vírus de DNA/patogenicidade , Filogenia , Archaea/virologia , Viés , Proteínas do Capsídeo/metabolismo , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Metagenômica , Vibrio/virologiaRESUMO
The clinical outcome of SARS-CoV-2 infection varies widely between individuals. Machine learning models can support decision making in healthcare by assessing fatality risk in patients that do not yet show severe signs of COVID-19. Most predictive models rely on static demographic features and clinical values obtained upon hospitalization. However, time-dependent biomarkers associated with COVID-19 severity, such as antibody titers, can substantially contribute to the development of more accurate outcome models. Here we show that models trained on immune biomarkers, longitudinally monitored throughout hospitalization, predicted mortality and were more accurate than models based on demographic and clinical data upon hospital admission. Our best-performing predictive models were based on the temporal analysis of anti-SARS-CoV-2 Spike IgG titers, white blood cell (WBC), neutrophil and lymphocyte counts. These biomarkers, together with C-reactive protein and blood urea nitrogen levels, were found to correlate with severity of disease and mortality in a time-dependent manner. Shapley additive explanations of our model revealed the higher predictive value of day post-symptom onset (PSO) as hospitalization progresses and showed how immune biomarkers contribute to predict mortality. In sum, we demonstrate that the kinetics of immune biomarkers can inform clinical models to serve as a powerful monitoring tool for predicting fatality risk in hospitalized COVID-19 patients, underscoring the importance of contextualizing clinical parameters according to their time post-symptom onset.
Assuntos
Anticorpos Antivirais/sangue , COVID-19 , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/terapia , Biologia Computacional , Diagnóstico por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: Bacterial swarming, a collective movement on a surface, has rarely been associated with human pathophysiology. This study aims to define a role for bacterial swarmers in amelioration of intestinal stress. METHODS: We developed a polymicrobial plate agar assay to detect swarming and screened mice and humans with intestinal stress and inflammation. From chemically induced colitis in mice, as well as humans with inflammatory bowel disease, we developed techniques to isolate the dominant swarmers. We developed swarm-deficient but growth and swim-competent mutant bacteria as isogenic controls. We performed bacterial reinoculation studies in mice with colitis, fecal 16S, and meta-transcriptomic analyses, as well as in vitro microbial interaction studies. RESULTS: We show that bacterial swarmers are highly predictive of intestinal stress in mice and humans. We isolated a novel Enterobacter swarming strain, SM3, from mouse feces. SM3 and other known commensal swarmers, in contrast to their mutant strains, abrogated intestinal inflammation in mice. Treatment of colitic mice with SM3, but not its mutants, enriched beneficial fecal anaerobes belonging to the family of Bacteroidales S24-7. We observed SM3 swarming associated pathways in the in vivo fecal meta-transcriptomes. In vitro growth of S24-7 was enriched in presence of SM3 or its mutants; however, because SM3, but not mutants, induced S24-7 in vivo, we concluded that swarming plays an essential role in disseminating SM3 in vivo. CONCLUSIONS: Overall, our work identified a new but counterintuitive paradigm in which intestinal stress allows for the emergence of swarming bacteria; however, these bacteria act to heal intestinal inflammation.
Assuntos
Colite/microbiologia , Enterobacter/fisiologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Técnicas Bacteriológicas , Colite/patologia , Colite/prevenção & controle , Modelos Animais de Doenças , Disbiose , Enterobacter/classificação , Fezes/microbiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Viabilidade Microbiana , Pessoa de Meia-Idade , Movimento , Probióticos , Reepitelização , Adulto JovemRESUMO
BACKGROUND: Inflammation is a crucial driver of host damage in patients with Clostridioides difficile colitis. We examined the potential for the intestinal microbiome to modify inflammation in patients with C. difficile colitis via the effects of gut-derived endotoxin on cytokine production. METHODS: Endotoxin from Escherichia coli and Pseudomonas aeruginosa as well as stool-derived endotoxin were tested for their ability to enhance interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) production by toxin B-stimulated peripheral blood mononuclear cells. Inflammasome and Toll-like receptor 4 (TLR4) blocking studies were done to discern the importance of these pathways, while metagenomic studies were done to characterize predominant organisms from stool samples. RESULTS: Endotoxin significantly enhanced the ability of C. difficile toxin B to promote IL-1ß production but not TNF-α. The magnitude of this effect varied by endotoxin type and was dependent on combined inflammasome and TLR4 activation. Stool-derived endotoxin exhibited a similar synergistic effect on IL-1ß production with less synergy observed for stools that contained a high proportion of γ-proteobacteria. CONCLUSIONS: The ability of endotoxin to enhance IL-1ß production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.
Assuntos
Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Clostridioides difficile/imunologia , Endotoxinas , Fezes/microbiologia , Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Interleucina-1beta/sangue , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Criança , Pré-Escolar , Clostridioides difficile/genética , Colite , Feminino , Humanos , Inflamassomos/sangue , Inflamação , Interleucina-1beta/metabolismo , Leucócitos Mononucleares , Masculino , Receptor 4 Toll-Like/sangueRESUMO
Postinfection irritable bowel syndrome (PI-IBS) is a diarrheal disease that develops after infectious gastroenteritis (IGE). Profound alterations in the microbiota accompany IGE yet only 10% of IGE patients progress to PI-IBS. This review explores research linking IGE severity, psychological comorbidity, PI-IBS, and the microbiome in various patient populations. Selective pressures caused by inflammation and increased gastrointestinal motility during gastroenteritis can alter intestinal bacterial phyla including Bacteroidetes, Firmicutes, and Proteobacteria. More specifically, classes such as Bacteroides and Clostridia are differentially abundant in many PI-IBS patients. Altered microbiota may perpetuate a cycle of enteric and systemic inflammation, potently activating neural afferent signaling in the enteric nervous system and causing pain and diarrhea in PI-IBS patients. Altered production of microbial metabolites, for example short chain fatty acids, may have enteric and systemic effects on the host. Longitudinal sampling to characterize changes in the microbiota's genetic, metabolic, and transcriptional activities over time from IGE to PI-IBS may enable improved diagnosis and classification of PI-IBS cases into subtypes, allowing for targeted antibiotic, probiotic, and prebiotic treatments. PI-IBS is a heterogenous and largely organic disease marked by specific alterations in functions of the microbiota and is an important model for studying microbial influences on intestinal, neurological, and psychological host functions.
Assuntos
Gastroenterite/complicações , Microbioma Gastrointestinal , Síndrome do Intestino Irritável/etiologia , Animais , Antibacterianos/administração & dosagem , Diarreia/etiologia , Diarreia/terapia , Gastroenterite/microbiologia , Humanos , Inflamação/microbiologia , Inflamação/patologia , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/terapia , Prebióticos/administração & dosagem , Probióticos/administração & dosagemRESUMO
ProPortal (http://proportal.mit.edu/) is a database containing genomic, metagenomic, transcriptomic and field data for the marine cyanobacterium Prochlorococcus. Our goal is to provide a source of cross-referenced data across multiple scales of biological organization--from the genome to the ecosystem--embracing the full diversity of ecotypic variation within this microbial taxon, its sister group, Synechococcus and phage that infect them. The site currently contains the genomes of 13 Prochlorococcus strains, 11 Synechococcus strains and 28 cyanophage strains that infect one or both groups. Cyanobacterial and cyanophage genes are clustered into orthologous groups that can be accessed by keyword search or through a genome browser. Users can also identify orthologous gene clusters shared by cyanobacterial and cyanophage genomes. Gene expression data for Prochlorococcus ecotypes MED4 and MIT9313 allow users to identify genes that are up or downregulated in response to environmental stressors. In addition, the transcriptome in synchronized cells grown on a 24-h light-dark cycle reveals the choreography of gene expression in cells in a 'natural' state. Metagenomic sequences from the Global Ocean Survey from Prochlorococcus, Synechococcus and phage genomes are archived so users can examine the differences between populations from diverse habitats. Finally, an example of cyanobacterial population data from the field is included.
Assuntos
Bacteriófagos/genética , Bases de Dados Genéticas , Prochlorococcus/genética , Genoma Bacteriano , Genoma Viral , Metagenômica , Família Multigênica , Prochlorococcus/virologia , Estresse Fisiológico/genética , Synechococcus/genética , Biologia de Sistemas , Integração de Sistemas , Transcrição GênicaRESUMO
Cyanophages infecting the marine cyanobacteria Prochlorococcus and Synechococcus encode and express genes for the photosynthetic light reactions. Sequenced cyanophage genomes lack Calvin cycle genes, however, suggesting that photosynthetic energy harvested via phage proteins is not used for carbon fixation. We report here that cyanophages carry and express a Calvin cycle inhibitor, CP12, whose host homologue directs carbon flux from the Calvin cycle to the pentose phosphate pathway (PPP). Phage CP12 was coexpressed with phage genes involved in the light reactions, deoxynucleotide biosynthesis, and the PPP, including a transaldolase gene that is the most prevalent PPP gene in cyanophages. Phage transaldolase was purified to homogeneity from several strains and shown to be functional in vitro, suggesting that it might facilitate increased flux through this key reaction in the host PPP, augmenting production of NADPH and ribose 5-phosphate. Kinetic measurements of phage and host transaldolases revealed that the phage enzymes have k(cat)/K(m) values only approximately one third of the corresponding host enzymes. The lower efficiency of phage transaldolase may be a tradeoff for other selective advantages such as reduced gene size: we show that more than half of host-like cyanophage genes are significantly shorter than their host homologues. Consistent with decreased Calvin cycle activity and increased PPP and light reaction activity under infection, the host NADPH/NADP ratio increased two-fold in infected cells. We propose that phage-augmented NADPH production fuels deoxynucleotide biosynthesis for phage replication, and that the selection pressures molding phage genomes involve fitness advantages conferred through mobilization of host energy stores.
Assuntos
Bacteriófagos/genética , Carbono/metabolismo , Cianobactérias/metabolismo , Genes Virais , Bacteriófagos/enzimologia , Cianobactérias/enzimologia , Cianobactérias/virologia , Cinética , Dados de Sequência Molecular , Transaldolase/metabolismo , Transcrição GênicaRESUMO
Viral genomes are poorly annotated in metagenomic samples, representing an obstacle to understanding viral diversity and function. Current annotation approaches rely on alignment-based sequence homology methods, which are limited by the paucity of characterized viral proteins and divergence among viral sequences. Here we show that protein language models can capture prokaryotic viral protein function, enabling new portions of viral sequence space to be assigned biologically meaningful labels. When applied to global ocean virome data, our classifier expanded the annotated fraction of viral protein families by 29%. Among previously unannotated sequences, we highlight the identification of an integrase defining a mobile element in marine picocyanobacteria and a capsid protein that anchors globally widespread viral elements. Furthermore, improved high-level functional annotation provides a means to characterize similarities in genomic organization among diverse viral sequences. Protein language models thus enhance remote homology detection of viral proteins, serving as a useful complement to existing approaches.
Assuntos
Células Procarióticas , Proteínas Virais , Proteínas Virais/genética , Genômica , Proteínas do Capsídeo/genética , MetagenômicaRESUMO
A decade ago, studies in human populations first revealed the existence of a unique microbial community in the breast, a tissue historically viewed as sterile, with microbial origins seeded through the nipple and/or translocation from other body sites. Since then, research efforts have been made to characterize the microbiome in healthy and cancerous breast tissues. The purpose of this review is to summarize the current evidence for the association of the breast microbiome with breast cancer risk and progression. Briefly, while many studies have examined the breast microbiome in patients with breast cancer, and compared it with the microbiome of benign breast disease tissue or normal breast tissue, these studies have varied widely in their sample sizes, methods, and quality of evidence. Thus, while several large and rigorous cross-sectional studies have provided key evidence of an altered microbiome in breast tumors compared with normal adjacent and healthy control tissue, there are few consistent patterns of perturbed microbial taxa. In addition, only one large prospective study has provided evidence of a relationship between the breast tumor microbiota and cancer prognosis. Future research studies featuring large, well-characterized cohorts with prospective follow-up for breast cancer incidence, progression, and response to treatment are warranted.
Assuntos
Neoplasias da Mama , Microbiota , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos Prospectivos , Estudos Transversais , Mama/patologiaRESUMO
Our understanding of secondary metabolite production in bacteria has been shaped primarily by studies of attached varieties such as symbionts, pathogens, and soil bacteria. Here we show that a strain of the single-celled, planktonic marine cyanobacterium Prochlorococcus-which conducts a sizable fraction of photosynthesis in the oceans-produces many cyclic, lanthionine-containing peptides (lantipeptides). Remarkably, in Prochlorococcus MIT9313 a single promiscuous enzyme transforms up to 29 different linear ribosomally synthesized peptides into a library of polycyclic, conformationally constrained products with highly diverse ring topologies. Genes encoding this system are found in variable abundances across the oceans-with a hot spot in a Galapagos hypersaline lagoon-suggesting they play a habitat- and/or community-specific role. The extraordinarily efficient pathway for generating structural diversity enables these cyanobacteria to produce as many secondary metabolites as model antibiotic-producing bacteria, but with much smaller genomes.
Assuntos
Biocatálise , Peptídeos Cíclicos/biossíntese , Fitoplâncton/metabolismo , Prochlorococcus/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência Conservada , Ciclização , Genoma Bacteriano , Dados de Sequência Molecular , Família Multigênica , Fitoplâncton/química , Fitoplâncton/genética , Prochlorococcus/química , Prochlorococcus/genética , Alinhamento de SequênciaRESUMO
Viral sequences are poorly annotated in environmental samples, a major roadblock to understanding how viruses influence microbial community structure. Current annotation approaches rely on alignment-based sequence ho-mology methods, which are limited by available viral sequences and sequence divergence in viral proteins. Here, we show that protein language model representations capture viral protein function beyond the limits of remote sequence homology by targeting two axes of viral sequence annotation: systematic labeling of protein families and function identification for biologic discovery. Protein language model representations capture protein functional properties specific to viruses and expand the annotated fraction of ocean virome viral protein sequences by 37%. Among unannotated viral protein families, we identify a novel DNA editing protein family that defines a new mobile element in marine picocyanobacteria. Protein language models thus significantly enhance remote homology detection of viral proteins and can be utilized to enable new biological discovery across diverse functional categories.
RESUMO
Helicobacter pylori is found in the gut lining of more than half of the world's population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis in H. pylori relies on the rare futalosine pathway, where H. pylori 5'-methylthioadenosine nucleosidase (MTAN) is proposed to play an essential role. Transition state analogues of MTAN, including BuT-DADMe-ImmA (BTDIA) and MeT-DADMe-ImmA (MTDIA), exhibit bacteriostatic action against numerous diverse clinical isolates of H. pylori with minimum inhibitory concentrations (MIC's) of <2 ng/mL. Three H. pylori BTDIA-resistant clones were selected under increasing BTDIA pressure. Whole genome sequencing showed no mutations in MTAN. Instead, resistant clones had mutations in metK, methionine adenosyltransferase (MAT), feoA, a regulator of the iron transport system, and flhF, a flagellar synthesis regulator. The mutation in metK causes expression of a MAT with increased catalytic activity, leading to elevated cellular S-adenosylmethionine. Metabolite analysis and the mutations associated with resistance suggest multiple inputs associated with BTDIA resistance. Human gut microbiome exposed to MTDIA revealed no growth inhibition under aerobic or anaerobic conditions. Transition state analogues of H. pylori MTAN have potential as agents for treating H. pylori infection without disruption of the human gut microbiome or inducing resistance in the MTAN target.
Assuntos
Helicobacter pylori , Humanos , Helicobacter pylori/genética , Purina-Núcleosídeo Fosforilase , N-Glicosil HidrolasesRESUMO
Tartrazine (E102, FD&C Yellow 5) is a vibrant yellow azo dye added to many processed foods. The safety of this ubiquitous chemical has not been fully elucidated, and it has been linked to allergic reactions and ADHD in some individuals. In our study, bacterial species isolated from human stool decolourised tartrazine and, upon exposure to air, a purple compound formed. Tartrazine is known to undergo reduction in the gut to sulfanilic acid and 4-amino-3-carboxy-5-hydroxy-1-(4-sulfophenyl)pyrazole (SCAP). These metabolites and their derivatives are relevant to the toxicology of tartrazine. The toxicity of sulfanilic acid has been studied before, but the oxidative instability of SCAP has previously prevented full characterisation. We have verified the chemical identity of SCAP and confirmed that the purple-coloured oxidation derivative is 4-(3-carboxy-5-hydroxy-1-(4-sulfophenyl)-1H-pyrazol-4-yl)imino-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (purpurazoic acid, PPA), as proposed by Westöö in 1965. A yellow derivative of SCAP is proposed to be the hydrolysed oxidation product, 4,5-dioxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid. SCAP and PPA are moderately toxic to human cells (IC50 89 and 78 µM against HEK-293, respectively), but had no apparent effect on Escherichia coli and Bacillus subtilis bacteria. These results prompt further analyses of the toxicology of tartrazine and its derivatives.
Assuntos
Compostos Azo , Tartrazina , Humanos , Tartrazina/toxicidade , Tartrazina/química , Compostos Azo/toxicidade , Células HEK293 , Oxirredução , Ácidos Carboxílicos , PirazóisRESUMO
Microbes of the human gut can change drug disposition in the human body and gut ecology via 'bioaccumulation', a process in which bacteria take up compounds intracellularly without chemically modifying them or experiencing changes in growth, as described in Klünemann et al. This work expands current understanding of the types of drug-bacterial interactions in the gut environment.
Assuntos
Microbioma Gastrointestinal , Microbiota , Bactérias , Bioacumulação , Interações Medicamentosas , HumanosRESUMO
Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H2S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H2S accumulation in vivo. Cryptic H2S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.
Assuntos
Sulfeto de Hidrogênio , Microbiota , Humanos , Masculino , Camundongos , Animais , Sulfeto de Hidrogênio/metabolismo , Xenobióticos/metabolismo , Bactérias/metabolismo , Oxirredução , Sulfetos/metabolismo , Enxofre/metabolismo , Compostos Azo/metabolismo , Escherichia coli/metabolismo , Corantes/metabolismoRESUMO
Microbial communities are shaped by viral predators. Yet, resolving which viruses (phages) and bacteria are interacting is a major challenge in the context of natural levels of microbial diversity. Thus, fundamental features of how phage-bacteria interactions are structured and evolve in the wild remain poorly resolved. Here we use large-scale isolation of environmental marine Vibrio bacteria and their phages to obtain estimates of strain-level phage predator loads, and use all-by-all host range assays to discover how phage and host genomic diversity shape interactions. We show that lytic interactions in environmental interaction networks (as observed in agar overlay) are sparse-with phage predator loads being low for most bacterial strains, and phages being host-strain-specific. Paradoxically, we also find that although overlap in killing is generally rare between tailed phages, recombination is common. Together, these results suggest that recombination during cryptic co-infections is an important mode of phage evolution in microbial communities. In the development of phages for bioengineering and therapeutics it is important to consider that nucleic acids of introduced phages may spread into local phage populations through recombination, and that the likelihood of transfer is not predictable based on lytic host range.
Assuntos
Bactérias/genética , Bactérias/virologia , Bacteriófagos/genética , Variação Genética , Genoma Viral , Especificidade de Hospedeiro , Modelos Biológicos , Nucleotídeos/metabolismo , Filogenia , Recombinases/metabolismo , Recombinação Genética/genética , Análise de Sequência de DNA , Vibrio/virologiaRESUMO
The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of SARS-CoV-2 genomes across the Bronx from March-October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of variants, we found that while some became 'endemic' to the Bronx, other, novel variants rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic. One sentence summary: Temporally and geographically resolved sequencing of SARS-CoV-2 genotypes enabled surveillance of novel genotypes, identification of endemic viral variants, and clinical inferences, in the first wave of the COVID-19 pandemic in the Bronx.
RESUMO
The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of 104 SARS-CoV-2 genomes across the Bronx from March October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of mutations, we found that while some became 'endemic' to the Bronx, other, novel mutations rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic.