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1.
Immunity ; 54(7): 1366-1368, 2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34260882

RESUMEN

Cells can detect pathogens through guard proteins that sense disturbances in core cellular processes, but the exact mechanisms often remain elusive. In this issue of Immunity, Orzalli et al. identify Bcl-2 family members as guard proteins that detect virus-induced translational inhibition and induce pyroptosis in human keratinocytes.


Asunto(s)
Queratinocitos , Piroptosis , Humanos
2.
Bioessays ; 45(10): e2300043, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37522605

RESUMEN

Meet the Metaorganism is a web-based learning app that combines three fundamental biological concepts (coevolution, community dynamics, and immune system) with latest scientific findings using the metaorganism as a central case study. In a transdisciplinary team of scientists, information designers, programmers, science communicators, and educators, we conceptualized and developed the app according to the latest didactic and scientific findings and aimed at setting new standards in visual design, digital knowledge transfer, and online education. A content management system allows continuous integration of new findings, which enables us to expand the app with the dynamics of the research field. Students can thus gain a close insight and connection to current research, and at the same time learn that knowledge is not static but grows dynamically. Especially in the realm of the easily accessible metaorganism research, visualization plays an essential role to keep complex processes understandable and memorable. Meet the Metaorganism is freely available online and can be accessed here: www.metaorganism.app.


Asunto(s)
Aplicaciones Móviles , Humanos , Estudiantes , Aprendizaje , Internet , Biología
3.
Anal Chem ; 95(48): 17550-17558, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-37984857

RESUMEN

Spectral similarity networks, also known as molecular networks, are crucial in non-targeted metabolomics to aid identification of unknowns aiming to establish a potential structural relation between different metabolite features. However, too extensive differences in compound structures can lead to separate clusters, complicating annotation. To address this challenge, we developed an automated Annotation Propagation through multiple EXperimental Networks (APEX) workflow, which integrates spectral similarity networks with mass difference networks and homologous series. The incorporation of multiple network tools improved annotation quality, as evidenced by high matching rates of the molecular formula derived by SIRIUS. The selection of manual annotations as the Seed Nodes Set (SNS) significantly influenced APEX annotations, with a higher number of seed nodes enhancing the annotation process. We applied APEX to different Caenorhabditis elegans metabolomics data sets as a proof-of-principle for the effective and comprehensive annotation of glycerophospho N-acyl ethanolamides (GPNAEs) and their glyco-variants. Furthermore, we demonstrated the workflow's applicability to two other, well-described metabolite classes in C. elegans, specifically ascarosides and modular glycosides (MOGLs), using an additional publicly available data set. In summary, the APEX workflow presents a powerful approach for metabolite annotation and identification by leveraging multiple experimental networks. By refining the SNS selection and integrating diverse networks, APEX holds promise for comprehensive annotation in metabolomics research, enabling a deeper understanding of the metabolome.


Asunto(s)
Caenorhabditis elegans , Metabolómica , Animales , Flujo de Trabajo , Metaboloma
4.
PLoS Pathog ; 17(4): e1009454, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33793670

RESUMEN

In C. elegans, 283 clec genes encode a highly diverse family of C-type lectin-like domain (CTLD) proteins. Since vertebrate CTLD proteins have characterized functions in defense responses against pathogens and since expression of C. elegans clec genes is pathogen-dependent, it is generally assumed that clec genes function in C. elegans immune defenses. However, little is known about the relative contribution and exact function of CLEC proteins in C. elegans immunity. Here, we focused on the C. elegans clec gene clec-4, whose expression is highly upregulated by pathogen infection, and its paralogs clec-41 and clec-42. We found that, while mutation of clec-4 resulted in enhanced resistance to the Gram-positive pathogen Bacillus thuringiensis MYBt18247 (Bt247), inactivation of clec-41 and clec-42 by RNAi enhanced susceptibility to Bt247. Further analyses revealed that enhanced resistance of clec-4 mutants to Bt247 was due to an increase in feeding cessation on the pathogen and consequently a decrease in pathogen load. Moreover, clec-4 mutants exhibited feeding deficits also on non-pathogenic bacteria that were in part reflected in the clec-4 gene expression profile, which overlapped with gene sets affected by starvation or mutation in nutrient sensing pathways. However, loss of CLEC-4 function only mildly affected life-history traits such as fertility, indicating that clec-4 mutants are not subjected to dietary restriction. While CLEC-4 function appears to be associated with the regulation of feeding behavior, we show that CLEC-41 and CLEC-42 proteins likely function as bona fide immune effector proteins that have bacterial binding and antimicrobial capacities. Together, our results exemplify functional diversification within clec gene paralogs.


Asunto(s)
Bacillus thuringiensis/fisiología , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Lectinas Tipo C/metabolismo , Transcriptoma , Animales , Caenorhabditis elegans/inmunología , Caenorhabditis elegans/microbiología , Proteínas de Caenorhabditis elegans/genética , Conducta Alimentaria , Inmunidad , Lectinas Tipo C/genética , Mutación con Pérdida de Función , Dominios Proteicos , Interferencia de ARN , Regulación hacia Arriba
5.
PLoS Pathog ; 16(9): e1008826, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32970778

RESUMEN

The nematode Caenorhabditis elegans has been extensively used as a model for the study of innate immune responses against bacterial pathogens. While it is well established that the worm mounts distinct transcriptional responses to different bacterial species, it is still unclear in how far it can fine-tune its response to different strains of a single pathogen species, especially if the strains vary in virulence and infection dynamics. To rectify this knowledge gap, we systematically analyzed the C. elegans response to two strains of Bacillus thuringiensis (Bt), MYBt18247 (Bt247) and MYBt18679 (Bt679), which produce different pore forming toxins (PFTs) and vary in infection dynamics. We combined host transcriptomics with cytopathological characterizations and identified both a common and also a differentiated response to the two strains, the latter comprising almost 10% of the infection responsive genes. Functional genetic analyses revealed that the AP-1 component gene jun-1 mediates the common response to both Bt strains. In contrast, the strain-specific response is mediated by the C. elegans GATA transcription factor ELT-2, a homolog of Drosophila SERPENT and vertebrate GATA4-6, and a known master regulator of intestinal responses in the nematode. elt-2 RNAi knockdown decreased resistance to Bt679, but remarkably, increased survival on Bt247. The elt-2 silencing-mediated increase in survival was characterized by reduced intestinal tissue damage despite a high pathogen burden and might thus involve increased tolerance. Additional functional genetic analyses confirmed the involvement of distinct signaling pathways in the C. elegans defense response: the p38-MAPK pathway acts either directly with or in parallel to elt-2 in mediating resistance to Bt679 infection but is not required for protection against Bt247. Our results further suggest that the elt-2 silencing-mediated increase in survival on Bt247 is multifactorial, influenced by the nuclear hormone receptors NHR-99 and NHR-193, and may further involve lipid metabolism and detoxification. Our study highlights that the nematode C. elegans with its comparatively simple immune defense system is capable of generating a differentiated response to distinct strains of the same pathogen species. Importantly, our study provides a molecular insight into the diversity of biological processes that are influenced by a single master regulator and jointly determine host survival after pathogen infection.


Asunto(s)
Bacillus thuringiensis/metabolismo , Infecciones Bacterianas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Factores de Transcripción GATA/metabolismo , Sistema de Señalización de MAP Quinasas , Transcripción Genética , Animales , Bacillus thuringiensis/patogenicidad , Infecciones Bacterianas/genética , Infecciones Bacterianas/microbiología , Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiología , Proteínas de Caenorhabditis elegans/genética , Factores de Transcripción GATA/genética
6.
Proteomics ; 18(8): e1700426, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29513928

RESUMEN

The nematode Caenorhabditis elegans interacts with a variety of bacteria as it feeds on microbes, and a number of these both associate and persist within the worm's intestine. Host-microbe interactions in C. elegans have been analyzed primarily at the transcriptome level with the host response often been monitored after challenge with pathogens. We assessed the proteome of C. elegans after growth on bacteria capable of colonizing its gut, via a comparative analysis of the nematode exposed to two naturally associated Ochrobactrum spp. (MYb71, MYb237) versus C. elegans grown on Escherichia coli OP50. A total of 4677 C. elegans proteins were identified, 3941 quantified. Significant alterations in protein abundances were observed for 122 proteins, 48 higher and 74 lower in abundance. We observed an increase in abundance of proteins potentially regulated via host signaling pathways, in addition to proteins involved in processing of foreign entities (e.g., lipase, proteases, glutathione metabolism). Decreased in abundance were proteins involved in both degradation and biosynthesis of amino acids, and enzymes associated with the degradation of peptidoglycan (lysozymes). The protein level differences between C. elegans grown on native microbiome members compared to the laboratory food bacterium may help to identify molecular processes involved in host-microbe interactions.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiología , Escherichia coli/fisiología , Infecciones por Bacterias Gramnegativas/veterinaria , Interacciones Huésped-Patógeno , Microbiota , Ochrobactrum/fisiología , Animales , Caenorhabditis elegans/metabolismo , Infecciones por Bacterias Gramnegativas/metabolismo , Proteómica , Transducción de Señal , Espectrometría de Masas en Tándem
7.
Bioinformatics ; 32(6): 943-5, 2016 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-26559506

RESUMEN

MOTIVATION: A particular challenge of the current omics age is to make sense of the inferred differential expression of genes and proteins. The most common approach is to perform a gene ontology (GO) enrichment analysis, thereby relying on a database that has been extracted from a variety of organisms and that can therefore only yield reliable information on evolutionary conserved functions. RESULTS: We here present a web-based application for a taxon-specific gene set exploration and enrichment analysis, which is expected to yield novel functional insights into newly determined gene sets. The approach is based on the complete collection of curated high-throughput gene expression data sets for the model nematode Caenorhabditis elegans, including 1786 gene sets from more than 350 studies. AVAILABILITY AND IMPLEMENTATION: WormExp is available at http://wormexp.zoologie.uni-kiel.de CONTACTS: hschulenburg@zoologie.uni-kiel.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Caenorhabditis elegans , Animales , Bases de Datos Factuales , Perfilación de la Expresión Génica , Internet , Programas Informáticos
8.
BMC Genomics ; 17: 280, 2016 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-27066825

RESUMEN

BACKGROUND: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. RESULTS: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. CONCLUSIONS: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.


Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Inmunidad Innata/genética , Sitios de Carácter Cuantitativo , Receptores de Neuropéptido Y/genética , Animales , Bacillus thuringiensis , Caenorhabditis elegans/inmunología , Caenorhabditis elegans/microbiología , Pseudomonas aeruginosa , Transducción de Señal , Transcriptoma
9.
J Invertebr Pathol ; 133: 34-40, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26592941

RESUMEN

In bacterial pathogens, virulence factors are often carried on plasmids and other mobile genetic elements, and as such, plasmid evolution is central in understanding pathogenicity. Bacillus thuringiensis is an invertebrate pathogen that uses plasmid-encoded crystal (Cry) toxins to establish infections inside the host. Our study aimed to quantify stability of two Cry toxin-encoding plasmids, BTI_23p and BTI_16p, under standard laboratory culturing conditions. These two plasmids are part of the genome of the B. thuringiensis strain MYBT18679, which is of particular interest because of its high pathogenicity towards nematodes. One of the plasmids, BTI_23p, was found to be highly unstable, with substantial loss occurring within a single growth cycle. Nevertheless, longer term experimental evolution in the absence of a host revealed maintenance of the plasmid at low levels in the bacterial populations. BTI_23p encodes two nematicidal Cry toxins, Cry21Aa2 and Cry14Aa1. Consistent with previous findings, loss of the plasmid abolished pathogenicity towards the nematode Caenorhabditis elegans, which could be rescued by addition of Cry21Aa2-expressing Escherichia coli. These results implicate BTI_23p as a plasmid that is required for successful infection, yet unstable when present at high frequency in the population, consistent with the role of Cry toxins as public goods.


Asunto(s)
Bacillus thuringiensis/patogenicidad , Proteínas Bacterianas/genética , Caenorhabditis elegans/microbiología , Endotoxinas/genética , Proteínas Hemolisinas/genética , Plásmidos/genética , Animales , Antinematodos/química , Antinematodos/farmacología , Bacillus thuringiensis/genética , Bacillus thuringiensis/fisiología , Toxinas de Bacillus thuringiensis , Caenorhabditis elegans/efectos de los fármacos , Escherichia coli/genética , Interacciones Huésped-Patógeno , Plásmidos/fisiología , Virulencia/genética
10.
mBio ; 15(4): e0346323, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38411078

RESUMEN

The Caenorhabditis elegans natural microbiota isolates Pseudomonas lurida MYb11 and Pseudomonas fluorescens MYb115 protect the host against pathogens through distinct mechanisms. While P. lurida produces an antimicrobial compound and directly inhibits pathogen growth, P. fluorescens MYb115 protects the host without affecting pathogen growth. It is unknown how these two protective microbes affect host biological processes. We used a proteomics approach to elucidate the C. elegans response to MYb11 and MYb115. We found that both Pseudomonas isolates increase vitellogenin protein production in young adults, which confirms previous findings on the effect of microbiota on C. elegans reproductive timing. Moreover, the C. elegans responses to MYb11 and MYb115 exhibit common signatures with the response to other vitamin B12-producing bacteria, emphasizing the importance of vitamin B12 in C. elegans-microbe metabolic interactions. We further analyzed signatures in the C. elegans response specific to MYb11 or MYb115. We provide evidence for distinct modifications in lipid metabolism by both symbiotic microbes. We could identify the activation of host-pathogen defense responses as an MYb11-specific proteome signature and provide evidence that the intermediate filament protein IFB-2 is required for MYb115-mediated protection. These results indicate that MYb11 not only produces an antimicrobial compound but also activates host antimicrobial defenses, which together might increase resistance to infection. In contrast, MYb115 affects host processes such as lipid metabolism and cytoskeleton dynamics, which might increase host tolerance to infection. Overall, this study pinpoints proteins of interest that form the basis for additional exploration into the mechanisms underlying C. elegans microbiota-mediated protection from pathogen infection and other microbiota-mediated traits.IMPORTANCESymbiotic bacteria can defend their host against pathogen infection. While some protective symbionts directly interact with pathogenic bacteria, other protective symbionts elicit a response in the host that improves its own pathogen defenses. To better understand how a host responds to protective symbionts, we examined which host proteins are affected by two protective Pseudomonas bacteria in the model nematode Caenorhabditis elegans. We found that the C. elegans response to its protective symbionts is manifold, which was reflected in changes in proteins that are involved in metabolism, the immune system, and cell structure. This study provides a foundation for exploring the contribution of the host response to symbiont-mediated protection from pathogen infection.


Asunto(s)
Antiinfecciosos , Proteínas de Caenorhabditis elegans , Animales , Caenorhabditis elegans/microbiología , Proteoma/metabolismo , Pseudomonas/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Antiinfecciosos/metabolismo , Vitaminas
11.
Microbiol Spectr ; 12(2): e0114423, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38230938

RESUMEN

While numerous health-beneficial interactions between host and microbiota have been identified, there is still a lack of targeted approaches for modulating these interactions. Thus, we here identify precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In the first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we use metabolic modeling to identify precision prebiotics for a two-member Caenorhabditis elegans microbiome community comprising the immune-protective target species Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. We experimentally confirm four of the predicted precision prebiotics, L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid, to specifically increase the abundance of MYb11. L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.IMPORTANCEWhile various mechanisms through which the microbiome influences disease processes in the host have been identified, there are still only few approaches that allow for targeted manipulation of microbiome composition as a first step toward microbiome-based therapies. Here, we propose the concept of precision prebiotics that allow to boost the abundance of already resident health-beneficial microbial species in a microbiome. We present a constraint-based modeling pipeline to predict precision prebiotics for a minimal microbial community in the worm Caenorhabditis elegans comprising the host-beneficial Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71 with the aim to boost the growth of MYb11. Experimentally testing four of the predicted precision prebiotics, we confirm that they are specifically able to increase the abundance of MYb11 in vitro and in vivo. These results demonstrate that constraint-based modeling could be an important tool for the development of targeted microbiome-based therapies against human diseases.


Asunto(s)
Microbiota , Prebióticos , Pseudomonas , Animales , Humanos , Caenorhabditis elegans , Serina
12.
bioRxiv ; 2023 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-36824941

RESUMEN

The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of interest. Moreover, current approaches for microbiome manipulation such as fecal transfers often entail a non-specific transfer of entire microbial communities with potentially unwanted side effects. To overcome this limitation, we here propose the concept of precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In a first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we present a metabolic modeling network framework that allows us to define precision prebiotics for a two-member C. elegans microbiome model community comprising the immune-protective Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. Thus, we predicted compounds that specifically boost the abundance of the host-beneficial MYb11, four of which were experimentally validated in vitro (L-serine, L-threonine, D-mannitol, and γ-aminobutyric acid). L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that constraint-based metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

13.
J Vis Exp ; (186)2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-36063004

RESUMEN

The nematode Caenorhabditis elegans interacts with a large diversity of microorganisms in nature. In general, C. elegans is commonly found in rotten plant matter, especially rotten fruits like apples or on compost heaps. It is also associated with certain invertebrate hosts such as slugs and woodlice. These habitats are rich in microbes, which serve as food for C. elegans and which can also persistently colonize the nematode gut. To date, the exact diversity and consistency of the native C. elegans microbiota across habitats and geographic locations is not fully understood. Here, we describe a suitable approach for isolating C. elegans from nature and characterizing the microbiota of worms. Nematodes can be easily isolated from compost material, rotting apples, slugs, or attracted by placing apples on compost heaps. The prime time for finding C. elegans in the Northern Hemisphere is from September until November. Worms can be washed out of collected substrate material by immersing the substrate in buffer solution, followed by the collection of nematodes and their transfer onto nematode growth medium or PCR buffer for subsequent analysis. We further illustrate how the samples can be used to isolate and purify the worm-associated microorganisms and to process worms for 16S ribosomal RNA analysis of microbiota community composition. Overall, the described methods may stimulate new research on the characterization of the C. elegans microbiota across habitats and geographic locations, thereby helping to obtain a comprehensive understanding of the diversity and stability of the nematode's microbiota as a basis for future functional research.


Asunto(s)
Malus , Microbiota , Animales , Caenorhabditis elegans/genética , Frutas , Malus/genética , ARN Ribosómico 16S/genética
14.
Front Cell Infect Microbiol ; 12: 775728, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35237530

RESUMEN

The Caenorhabditis elegans natural microbiota was described only recently. Thus, our understanding of its effects on nematode physiology is still in its infancy. We previously showed that the C. elegans natural microbiota isolates Pseudomonas lurida MYb11 and P. fluorescens MYb115 protect the worm against pathogens such as Bacillus thuringiensis (Bt). However, the overall effects of the protective microbiota on worm physiology are incompletely understood. Here, we investigated how MYb11 and MYb115 affect C. elegans lifespan, fertility, and intestinal colonization. We further studied the capacity of MYb11 and MYb115 to protect the worm against purified Bt toxins. We show that while MYb115 and MYb11 affect reproductive timing and increase early reproduction only MYb11 reduces worm lifespan. Moreover, MYb11 aggravates killing upon toxin exposure. We conclude that MYb11 has a pathogenic potential in some contexts. This work thus highlights that certain C. elegans microbiota members can be beneficial and costly to the host in a context-dependent manner, blurring the line between good and bad.


Asunto(s)
Bacillus thuringiensis , Proteínas de Caenorhabditis elegans , Microbiota , Animales , Caenorhabditis elegans , Intestinos
15.
Dev Comp Immunol ; 123: 104144, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34051205

RESUMEN

microRNAs (miRNAs) are small non-coding RNA-molecules that influence translation by binding to the target gene mRNA. Many miRNAs are found in nested arrangements within larger protein-coding host genes. miRNAs and host genes in a nested arrangement are often transcribed simultaneously, which may indicate that both have similar functions. miRNAs have been implicated in regulating defense responses against pathogen infection in C. elegans and in mammals. Here, we asked if miRNAs in nested arrangements and their host genes are involved in the C. elegans response against infection with Bacillus thuringiensis (Bt). We performed miRNA sequencing and subsequently focused on four nested miRNA-host gene arrangements for a functional genetic analysis. We identified mir-58.1 and mir-2 as negative regulators of C. elegans resistance to Bt infection. However, we did not find any miRNA/host gene pair in which both contribute to defense against Bt.


Asunto(s)
Bacillus thuringiensis/fisiología , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/inmunología , Infecciones por Bacterias Grampositivas/inmunología , MicroARNs/genética , Animales , Resistencia a la Enfermedad , Interacciones Huésped-Patógeno , Inmunidad Innata , Análisis de Secuencia de ARN
16.
Front Immunol ; 11: 1251, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32612612

RESUMEN

Multicellular organisms live in close association with a plethora of microorganism, which have a profound effect on multiple host functions. As such, the microbiota and its host form an intimate functional entity, termed the metaorganism or holobiont. But how does the metaorganism communicate? Which receptors recognize microbial signals, mediate the effect of the microbiota on host physiology or regulate microbiota composition and homeostasis? In this review we provide an overview on the function of different receptor classes in animal host-microbiota communication. We put a special focus on invertebrate hosts, including both traditional invertebrate models such as Drosophila melanogaster and Caenorhabditis elegans and "non-model" invertebrates in microbiota research. Finally, we highlight the potential of invertebrate systems in studying mechanism of host-microbiota interactions.


Asunto(s)
Interacciones Microbiota-Huesped , Microbiota , Receptores de Reconocimiento de Patrones/metabolismo , Transducción de Señal , Animales , Biodiversidad , Homeostasis , Interacciones Microbiota-Huesped/inmunología , Humanos , Invertebrados , Microbiota/inmunología , Unión Proteica , Especificidad de la Especie
17.
ISME J ; 14(1): 26-38, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31484996

RESUMEN

The microbiota is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiota of the model nematode Caenorhabditis elegans. We integrated whole-genome sequences of 77 bacterial microbiota members with metabolic modeling and experimental characterization of bacterial physiology. We found that, as a community, the microbiota can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses revealed that nutrient context can influence how bacteria interact within the microbiota. We identified key bacterial traits that are likely to influence the microbe's ability to colonize C. elegans (i.e., the ability of bacteria for pyruvate fermentation to acetoin) and affect nematode fitness (i.e., bacterial competence for hydroxyproline degradation). Considering that the microbiota is usually neglected in C. elegans research, the resource presented here will help our understanding of this nematode's biology in a more natural context. Our integrative approach moreover provides a novel, general framework to characterize microbiota-mediated functions.


Asunto(s)
Bacterias/metabolismo , Caenorhabditis elegans/microbiología , Microbiota , Animales , Bacterias/genética , Bacterias/aislamiento & purificación , Caenorhabditis elegans/metabolismo , Redes y Vías Metabólicas/genética
18.
Curr Biol ; 29(6): 1030-1037.e5, 2019 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-30827913

RESUMEN

Caenorhabditis elegans is associated in nature with a species-rich, distinct microbiota, which was characterized only recently [1]. Thus, our understanding of the relevance of the microbiota for nematode fitness is still at its infancy. One major benefit that the intestinal microbiota can provide to its host is protection against pathogen infection [2]. However, the specific strains conferring the protection and the underlying mechanisms of microbiota-mediated protection are often unclear [3]. Here, we identify natural C. elegans microbiota isolates that increase C. elegans resistance to pathogen infection. We show that isolates of the Pseudomonas fluorescens subgroup provide paramount protection from infection with the natural pathogen Bacillus thuringiensis through distinct mechanisms. We found that the P. lurida isolates MYb11 and MYb12 (members of the P. fluorescens subgroup) protect C. elegans against B. thuringiensis infection by directly inhibiting growth of the pathogen both in vitro and in vivo. Using genomic and biochemical analyses, we further demonstrate that MYb11 and MYb12 produce massetolide E, a cyclic lipopeptide biosurfactant of the viscosin group [4, 5], which is active against pathogenic B. thuringiensis. In contrast to MYb11 and MYb12, P. fluorescens MYb115-mediated protection involves increased resistance without inhibition of pathogen growth and most likely depends on indirect, host-mediated mechanisms. This work provides new insight into the functional significance of the C. elegans natural microbiota and expands our knowledge of bacteria-derived compounds that can influence pathogen colonization in the intestine of an animal.


Asunto(s)
Bacillus thuringiensis/fisiología , Caenorhabditis elegans/microbiología , Interacciones Huésped-Patógeno , Lipopéptidos/metabolismo , Microbiota , Péptidos Cíclicos/metabolismo , Pseudomonas/química , Animales
19.
Front Microbiol ; 10: 1793, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31440221

RESUMEN

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiota affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematode Caenorhabditis elegans as a tractable, experimental model system and assessed the inducible transcriptome response after colonization with members of its native microbiota. For this study, we focused on two isolates of the genus Ochrobactrum. These bacteria are known to be abundant in the nematode's microbiota and are capable of colonizing and persisting in the nematode gut, even under stressful conditions. The transcriptome response was assessed across development and three time points of adult life, using general and C. elegans-specific enrichment analyses to identify affected functions. Our assessment revealed an influence of the microbiota members on the nematode's dietary response, development, fertility, immunity, and energy metabolism. This response is mainly regulated by a GATA transcription factor, most likely ELT-2, as indicated by the enrichment of (i) the GATA motif in the promoter regions of inducible genes and (ii) of ELT-2 targets among the differentially expressed genes. We compared our transcriptome results with a corresponding previously characterized proteome data set, highlighting a significant overlap in the differentially expressed genes, the affected functions, and ELT-2 target genes. Our analysis further identified a core set of 86 genes that consistently responded to the microbiota members across development and adult life, including several C-type lectin-like genes and genes known to be involved in energy metabolism or fertility. We additionally assessed the consequences of induced gene expression with the help of metabolic network model analysis, using a previously established metabolic network for C. elegans. This analysis complemented the enrichment analyses by revealing an influence of the Ochrobactrum isolates on C. elegans energy metabolism and furthermore metabolism of specific amino acids, fatty acids, and also folate biosynthesis. Our findings highlight the multifaceted impact of naturally colonizing microbiota isolates on C. elegans life history and thereby provide a framework for further analysis of microbiota-mediated host functions.

20.
Microbiome ; 7(1): 133, 2019 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-31521200

RESUMEN

BACKGROUND: The interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution, and development of both players. These interdependencies inspired a new view of multicellular organisms as "metaorganisms." The goal of the Collaborative Research Center "Origin and Function of Metaorganisms" is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants. METHODS: In order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample. CONCLUSION: While 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Overall, we recommend single- over multi-step amplification procedures, and although exceptions and trade-offs exist, the V3 V4 over the V1 V2 region of the 16S rRNA gene. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenoma/fisiología , Microbiota/fisiología , ARN Ribosómico 16S/genética , Animales , Bacterias/clasificación , Bacterias/genética , Bases de Datos Genéticas , Humanos , Metagenoma/genética , Microbiota/genética , Filogenia
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