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Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.
Assuntos
Antibacterianos , Escherichia coli , Humanos , Animais , Camundongos , Cefepima , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Trato Gastrointestinal/microbiologia , Polissacarídeos , Testes de Sensibilidade Microbiana , MamíferosRESUMO
Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the variable of coinfection order in a system of gammaherpesvirus-helminth coinfection. Our previous work demonstrated that infection with the intestinal parasite, Heligmosomoides polygyrus, induced transient reactivation from latency of murine gammaherpesvirus-68 (MHV68). In this report, we reverse the order of coinfection, infecting with H. polygyrus first, followed by MHV68, and examined the effects of preexisting parasite infection on MHV68 acute and latent infection. We found that preexisting parasite infection increased the propensity of MHV68 to reactivate from latency. However, when we examined the mechanism for reactivation, we found that preexisting parasite infection increased the ability of MHV68 to reactivate in a vitamin A dependent manner, a distinct mechanism to what we found previously with parasite-induced reactivation after latency establishment. We determined that H. polygyrus infection increased both acute and latent MHV68 infection in a population of tissue resident macrophages, called large peritoneal macrophages. We demonstrate that this population of macrophages and vitamin A are required for increased acute and latent infection during parasite coinfection.
Assuntos
Coinfecção , Gammaherpesvirinae , Helmintos , Infecções por Herpesviridae , Infecção Latente , Doenças Parasitárias , Humanos , Animais , Camundongos , Ativação Viral , Latência Viral/fisiologia , Vitamina A , Linfócitos B , Infecções por Herpesviridae/complicações , Gammaherpesvirinae/fisiologia , Macrófagos , Camundongos Endogâmicos C57BLRESUMO
Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells. Disruption of the RORγt-Raftlin1 complex results in the reduction of pathogenic Th17 cells in response to Citrobacter rodentium; however, there is no effect on nonpathogenic Th17 cells in response to commensal segmented filamentous bacteria. Mechanistically, we show that Raftlin1 recruits distinct phospholipids to RORγt and promotes the pathogenicity of Th17 cells. Thus, we have identified a mechanism that drives the pathogenic function of Th17 cells, which could provide a platform for advanced therapeutic strategies to dampen Th17-mediated inflammatory diseases.
Assuntos
Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Células Th17 , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Virulência , Inflamação , ColoRESUMO
The intestinal microbiota regulates mammalian lipid absorption, metabolism, and storage. We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA (lncRNA) Snhg9 (small nucleolar RNA host gene 9) in small intestinal epithelial cells. Snhg9 suppressed the activity of peroxisome proliferator-activated receptor γ (PPARγ)-a central regulator of lipid metabolism-by dissociating the PPARγ inhibitor sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice impaired lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune relay encompassing myeloid cells and group 3 innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.
Assuntos
Microbioma Gastrointestinal , Intestinos , Metabolismo dos Lipídeos , PPAR gama , RNA Longo não Codificante , Sirtuína 1 , Animais , Camundongos , Imunidade Inata , Metabolismo dos Lipídeos/genética , Linfócitos/imunologia , PPAR gama/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuína 1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Células Mieloides/imunologia , Intestinos/metabolismo , Intestinos/microbiologia , Tecido Adiposo/microbiologia , HumanosRESUMO
Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here, we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates the complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for the immune defense of the intestine. Instead, C1q-expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they were closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.
Assuntos
Complemento C1q , Sistema Nervoso Entérico , Camundongos , Animais , Complemento C1q/metabolismo , Motilidade Gastrointestinal/fisiologia , Macrófagos/metabolismo , Trato GastrointestinalRESUMO
Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.
Assuntos
Microbioma Gastrointestinal , Melanoma , Humanos , Inibidores de Checkpoint Imunológico , Linfócitos T CD8-Positivos , LinfonodosRESUMO
Immunoglobulin A (IgA) secretion by plasma cells, terminally differentiated B cells residing in the intestinal lamina propria, assures microbiome homeostasis and protects the host against enteric infections. Exposure to diet-derived and commensal-derived signals provides immune cells with organizing cues that instruct their effector function and dynamically shape intestinal immune responses at the mucosal barrier. Recent data have described metabolic and microbial inputs controlling T cell and innate lymphoid cell activation in the gut; however, whether IgA-secreting lamina propria plasma cells are tuned by local stimuli is completely unknown. Although antibody secretion is considered to be imprinted during B cell differentiation and therefore largely unaffected by environmental changes, a rapid modulation of IgA levels in response to intestinal fluctuations might be beneficial to the host. In the present study, we showed that dietary cholesterol absorption and commensal recognition by duodenal intestinal epithelial cells lead to the production of oxysterols, evolutionarily conserved lipids with immunomodulatory functions. Using conditional cholesterol 25-hydroxylase deleter mouse line we demonstrated that 7α,25-dihydroxycholesterol from epithelial cells is critical to restrain IgA secretion against commensal- and pathogen-derived antigens in the gut. Intestinal plasma cells sense oxysterols via the chemoattractant receptor GPR183 and couple their tissue positioning with IgA secretion. Our findings revealed a new mechanism linking dietary cholesterol and humoral immune responses centered around plasma cell localization for efficient mucosal protection.
Assuntos
Imunidade Inata , Plasmócitos , Animais , Camundongos , Colesterol na Dieta , Células Epiteliais , Imunoglobulina A , Mucosa Intestinal , Receptores Acoplados a Proteínas G , IntestinosRESUMO
In vitro systems have provided great insight into the mechanisms of antibiotic resistance. Yet, in vitro approaches cannot reflect the full complexity of what transpires within a host. As the mammalian gut is host to trillions of resident bacteria and thus a potential breeding ground for antibiotic resistance, we sought to better understand how gut bacteria respond to antibiotic treatment in vivo . Here, we colonized germ-free mice with a genetically barcoded antibiotic pan-susceptible Escherichia coli clinical isolate and then administered the antibiotic cefepime via programmable subcutaneous pumps which allowed for closer emulation of human parenteral antibiotic pharmacokinetics/dynamics. After seven days of antibiotics, we were unable to culture E. coli from feces. We were, however, able to recover barcoded E. coli from harvested gastrointestinal (GI) tissue, despite high GI tract and plasma cefepime concentrations. Strikingly, these E. coli isolates were not resistant to cefepime but had acquired mutations â" most notably in the wbaP gene, which encodes an enzyme required for the initiation of the synthesis of the polysaccharide capsule and lipopolysaccharide O antigen - that increased their ability to invade and survive within intestinal cells, including cultured human colonocytes. Further, these E. coli mutants exhibited a persister phenotype when exposed to cefepime, allowing for greater survival to pulses of cefepime treatment when compared to the wildtype strain. Our findings highlight a mechanism by which bacteria in the gastrointestinal tract can adapt to antibiotic treatment by increasing their ability to persist during antibiotic treatment and invade intestinal epithelial cells where antibiotic concentrations are substantially reduced.
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High viral transmission in the COVID-19 pandemic has enabled SARS-CoV-2 to acquire new mutations that may impact genome sequencing methods. The ARTIC.v3 primer pool that amplifies short amplicons in a multiplex-PCR reaction is one of the most widely used methods for sequencing the SARS-CoV-2 genome. We observed that some genomic intervals are poorly captured with ARTIC primers. To improve the genomic coverage and variant detection across these intervals, we designed long amplicon primers and evaluated the performance of a short (ARTIC) plus long amplicon (MRL) sequencing approach. Sequencing assays were optimized on VR-1986D-ATCC RNA followed by sequencing of nasopharyngeal swab specimens from fifteen COVID-19 positive patients. ARTIC data covered 94.47% of the virus genome fraction in the positive control and patient samples. Variant analysis in the ARTIC data detected 217 mutations, including 209 single nucleotide variants (SNVs) and eight insertions & deletions. On the other hand, long-amplicon data detected 156 mutations, of which 80% were concordant with ARTIC data. Combined analysis of ARTIC + MRL data improved the genomic coverage to 97.03% and identified 214 high confidence mutations. The combined final set of 214 mutations included 203 SNVs, 8 deletions and 3 insertions. Analysis showed 26 SARS-CoV-2 lineage defining mutations including 4 known variants of concern K417N, E484K, N501Y, P618H in spike gene. Hybrid analysis identified 7 nonsynonymous and 5 synonymous mutations across the genome that were either ambiguous or not called in ARTIC data. For example, G172V mutation in the ORF3a protein and A2A mutation in Membrane protein were missed by the ARTIC assay. Thus, we show that while the short amplicon (ARTIC) assay provides good genomic coverage with high throughput, complementation of poorly captured intervals with long amplicon data can significantly improve SARS-CoV-2 genomic coverage and variant detection.
Assuntos
Genoma Viral/genética , Genômica/métodos , SARS-CoV-2/genética , Sequenciamento Completo do Genoma/métodos , COVID-19/virologia , Humanos , RNA Viral/genética , Análise de Sequência/métodosRESUMO
Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis. Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production. Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a ß1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains. Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
Assuntos
Células Epiteliais , Glicoproteínas , Interleucinas , Mucosa Intestinal , N-Acetilglucosaminiltransferases , Células Epiteliais/metabolismo , Glicoproteínas/metabolismo , Glicosilação , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , N-Acetilglucosaminiltransferases/biossíntese , N-Acetilglucosaminiltransferases/metabolismo , Polissacarídeos/metabolismo , Interleucina 22RESUMO
A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.
Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Microbioma Gastrointestinal , Bactérias Gram-Positivas/fisiologia , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Nematospiroides dubius , Infecções por Strongylida/imunologia , Animais , Carga Bacteriana , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Proteínas Ricas em Prolina do Estrato Córneo/genética , Citocinas/metabolismo , Suscetibilidade a Doenças , Células Caliciformes/metabolismo , Humanos , Imunidade Inata , Mucosa Intestinal/microbiologia , Listeria monocytogenes/fisiologia , Listeriose/microbiologia , Camundongos , Viabilidade Microbiana , Celulas de Paneth/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Infecções por Strongylida/metabolismo , Infecções por Strongylida/microbiologiaRESUMO
Bead-beating within a DNA extraction protocol is critical for complete microbial cell lysis and accurate assessment of the abundance and composition of the microbiome. While the impact of bead-beating on the recovery of OTUs at the phylum and class level have been studied, its influence on species-level microbiome recovery is not clear. Recent advances in sequencing technology has allowed species-level resolution of the microbiome using full length 16S rRNA gene sequencing instead of smaller amplicons that only capture a few hypervariable regions of the gene. We sequenced the v3-v4 hypervariable region as well as the full length 16S rRNA gene in mouse and human stool samples and discovered major clusters of gut bacteria that exhibit different levels of sensitivity to bead-beating treatment. Full length 16S rRNA gene sequencing unraveled vast species diversity in the mouse and human gut microbiome and enabled characterization of several unclassified OTUs in amplicon data. Many species of major gut commensals such as Bacteroides, Lactobacillus, Blautia, Clostridium, Escherichia, Roseburia, Helicobacter, and Ruminococcus were identified. Interestingly, v3-v4 amplicon data classified about 50% of Ruminococcus reads as Ruminococcus gnavus species which showed maximum abundance in a 9 min beaten sample. However, the remaining 50% of reads could not be assigned to any species. Full length 16S rRNA gene sequencing data showed that the majority of the unclassified reads were Ruminococcus albus species which unlike R. gnavus showed maximum recovery in the unbeaten sample instead. Furthermore, we found that the Blautia hominis and Streptococcus parasanguinis species were differently sensitive to bead-beating treatment than the rest of the species in these genera. Thus, the present study demonstrates species level variations in sensitivity to bead-beating treatment that could only be resolved with full length 16S rRNA sequencing. This study identifies species of common gut commensals and potential pathogens that require minimum (0-1 min) or extensive (4-9 min) bead-beating for their maximal recovery.
Assuntos
Microbioma Gastrointestinal , Animais , Clostridiales , DNA Bacteriano/genética , Genes de RNAr , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , RNA Ribossômico 16S/genética , Ruminococcus , Análise de Sequência de DNA , StreptococcusRESUMO
Vitamin A and its derivative retinol are essential for the development of intestinal adaptive immunity. Retinoic acid (RA)producing myeloid cells are central to this process, but how myeloid cells acquire retinol for conversion to RA is unknown. Here, we show that serum amyloid A (SAA) proteinsretinol-binding proteins induced in intestinal epithelial cells by the microbiotadeliver retinol to myeloid cells. We identify low-density lipoprotein (LDL) receptorrelated protein 1 (LRP1) as an SAA receptor that endocytoses SAA-retinol complexes and promotes retinol acquisition by RA-producing intestinal myeloid cells. Consequently, SAA and LRP1 are essential for vitamin Adependent immunity, including B and T cell homing to the intestine and immunoglobulin A production. Our findings identify a key mechanism by which vitamin A promotes intestinal immunity.
Assuntos
Imunidade Adaptativa , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Células Mieloides/metabolismo , Proteína Amiloide A Sérica/metabolismo , Vitamina A/metabolismo , Animais , Linfócitos B/imunologia , Antígeno CD11c/análise , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Endocitose , Deleção de Genes , Humanos , Imunoglobulina A/biossíntese , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/imunologia , Ligação Proteica , Proteínas de Ligação ao Retinol/metabolismo , Salmonelose Animal/imunologia , Salmonella typhimurium , Proteína Amiloide A Sérica/genética , Células Th17/imunologiaRESUMO
There is an increasing appreciation for the role of metabolism in cell signaling and cell decision making. Precise metabolic control is essential in development, as evident by the disorders caused by mutations in metabolic enzymes. The metabolic profile of cells is often cell-type specific, changing as cells differentiate or during tumorigenesis. Recent evidence has shown that changes in metabolism are not merely a consequence of changes in cell state but that metabolites can serve to promote and/or inhibit these changes. Metabolites can link metabolic pathways with cell signaling pathways via several mechanisms, for example, by serving as substrates for protein post-translational modifications, by affecting enzyme activity via allosteric mechanisms, or by altering epigenetic markers. Unraveling the complex interactions governing metabolism, gene expression, and protein activity that ultimately govern a cell's fate will require new tools and interactions across disciplines. On March 24 and 25, 2021, experts in cell metabolism, developmental biology, and human disease met virtually for the Keystone eSymposium, "Metabolic Decisions in Development and Disease." The discussions explored how metabolites impact cellular and developmental decisions in a diverse range of model systems used to investigate normal development, developmental disorders, dietary effects, and cancer-mediated changes in metabolism.
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Congressos como Assunto/tendências , Desenvolvimento Humano/fisiologia , Doenças Metabólicas/fisiopatologia , Redes e Vias Metabólicas/fisiologia , Neoplasias/fisiopatologia , Relatório de Pesquisa , Animais , Epigênese Genética/fisiologia , Humanos , Doenças Metabólicas/genética , Neoplasias/genética , Transdução de Sinais/fisiologiaRESUMO
Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.
Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Microbioma Gastrointestinal , Imunidade Inata , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Aderência Bacteriana , Adesão Celular , Células Epiteliais/microbiologia , Comportamento Alimentar , Intestino Delgado/microbiologia , Intestino Delgado/ultraestrutura , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Muramidase/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Fator de Transcrição STAT3/metabolismo , Salmonelose Animal/microbiologia , Transdução de SinaisRESUMO
BACKGROUND: Horizontal gene transfer (HGT) plays a central role in microbial evolution. Our understanding of the mechanisms, frequency, and taxonomic range of HGT in polymicrobial environments is limited, as we currently rely on historical HGT events inferred from genome sequencing and studies involving cultured microorganisms. We lack approaches to observe ongoing HGT in microbial communities. RESULTS: To address this knowledge gap, we developed a DNA sequencing-based "transductomics" approach that detects and characterizes microbial DNA transferred via transduction. We validated our approach using model systems representing a range of transduction modes and show that we can detect numerous classes of transducing DNA. Additionally, we show that we can use this methodology to obtain insights into DNA transduction among all major taxonomic groups of the intestinal microbiome. CONCLUSIONS: The transductomics approach that we present here allows for the detection and characterization of genes that are potentially transferred between microbes in complex microbial communities at the time of measurement and thus provides insights into real-time ongoing horizontal gene transfer. This work extends the genomic toolkit for the broader study of mobile DNA within microbial communities and could be used to understand how phenotypes spread within microbiomes. Video Abstract.
Assuntos
DNA Bacteriano/análise , DNA Bacteriano/genética , Transferência Genética Horizontal/genética , Genômica , Microbiota/genética , Transdução Genética , Animais , Microbioma Gastrointestinal/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos TestesRESUMO
The circadian clock couples physiological processes and behaviors to environmental light cycles. This coupling ensures the synchronization of energetically expensive processes to the time of day at which an organism is most active, thus improving overall fitness. Host immunity is an energetically intensive process that requires the coordination of multiple immune cell types to sense, communicate, and respond to a variety of microorganisms. Interestingly the circadian clock entrains immune cell development, function, and trafficking to environmental light cycles. This entrainment results in the variation of host susceptibility to microbial pathogens across the day-night cycle. In addition, the circadian clock engages in bi-directional communication with the microbiota, resident microorganisms that reside in proximity to the epithelial surfaces of animals. This bi-directional interchange plays an essential role in regulating host immunity and is also pivotal for the circadian control of metabolism. Here, we review the role of the circadian clock in directing host immune programs and consider how commensal and pathogenic microbes impact circadian physiological processes.