Take a Walk to the Wild Side of Caenorhabditis elegans-Pathogen Interactions

2021 ◽  
Vol 85 (2) ◽  
Author(s):  
Leah J. Radeke ◽  
Michael A. Herman
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Recent Work ◽  
Genetic Model ◽  
Model Organism ◽  
Bacterial Pathogen ◽  
Content Type ◽  
Microbiome Composition ◽  
C Elegans ◽  
Functional Studies

SUMMARY Microbiomes form intimate functional associations with their hosts. Much has been learned from correlating changes in microbiome composition to host organismal functions. However, in-depth functional studies require the manipulation of microbiome composition coupled with the precise interrogation of organismal physiology—features available in few host study systems. Caenorhabditis elegans has proven to be an excellent genetic model organism to study innate immunity and, more recently, microbiome interactions. The study of C. elegans-pathogen interactions has provided in depth understanding of innate immune pathways, many of which are conserved in other animals. However, many bacteria were chosen for these studies because of their convenience in the lab setting or their implication in human health rather than their native interactions with C. elegans. In their natural environment, C. elegans feed on a variety of bacteria found in rotting organic matter, such as rotting fruits, flowers, and stems. Recent work has begun to characterize the native microbiome and has identified a common set of bacteria found in the microbiome of C. elegans. While some of these bacteria are beneficial to C. elegans health, others are detrimental, leading to a complex, multifaceted understanding of bacterium-nematode interactions. Current research on nematode-bacterium interactions is focused on these native microbiome components, both their interactions with each other and with C. elegans. We will summarize our knowledge of bacterial pathogen-host interactions in C. elegans, as well as recent work on the native microbiome, and explore the incorporation of these bacterium-nematode interactions into studies of innate immunity and pathogenesis.

scholarly journals Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Don B. Gammon
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Fungal Pathogens ◽  
Model Organism ◽  
Artificial Infection ◽  
Viral Pathogen ◽  
Content Type ◽  
Host Interactions ◽  
C Elegans ◽  
Infection Models

ABSTRACT Since 1999, Caenorhabditis elegans has been extensively used to study microbe-host interactions due to its simple culture, genetic tractability, and susceptibility to numerous bacterial and fungal pathogens. In contrast, virus studies have been hampered by a lack of convenient virus infection models in nematodes. The recent discovery of a natural viral pathogen of C. elegans and development of diverse artificial infection models are providing new opportunities to explore virus-host interplay in this powerful model organism.

scholarly journals Caenorhabditis elegans, a Model Organism for Investigating Immunity

2012 ◽  
Vol 78 (7) ◽  
pp. 2075-2081 ◽  
Author(s):  
Elizabeth K. Marsh ◽  
Robin C. May
Keyword(s):  
Caenorhabditis Elegans ◽  
Viral Infections ◽  
Model Organism ◽  
Human Pathogens ◽  
Microsporidian Parasite ◽  
Content Type ◽  
C Elegans ◽  
Pathogen Virulence ◽  
The Past ◽  
Animal Hosts

ABSTRACTThe nematodeCaenorhabditis eleganshas been a powerful experimental organism for almost half a century. Over the past 10 years, researchers have begun to exploit the power ofC. elegansto investigate the biology of a number of human pathogens. This work has uncovered mechanisms of host immunity and pathogen virulence that are analogous to those involved during pathogenesis in humans or other animal hosts, as well as novel immunity mechanisms which appear to be unique to the worm. More recently, these investigations have uncovered details of the natural pathogens ofC. elegans, including the description of a novel intracellular microsporidian parasite as well as new nodaviruses, the first identification of viral infections of this nematode. In this review, we consider the application ofC. elegansto human infectious disease research, as well as consider the nematode response to these natural pathogens.

scholarly journals The Diabetes Autoantigen ICA69 and Its Caenorhabditis elegans Homologue, ric-19, Are Conserved Regulators of Neuroendocrine Secretion

2000 ◽  
Vol 11 (10) ◽  
pp. 3277-3288 ◽  
Author(s):  
Marc Pilon ◽  
Xiao-Rong Peng ◽  
Andrew M. Spence ◽  
Ronald H.A. Plasterk ◽  
Hans-Michael Dosch
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Secretory Activity ◽  
Subcellular Fractionation ◽  
Secretory Cells ◽  
Secretory Vesicles ◽  
Expression Levels ◽  
C Elegans ◽  
Functional Studies ◽  
Neurotransmitter Secretion

ICA69 is a diabetes autoantigen with no homologue of known function. Given that most diabetes autoantigens are associated with neuroendocrine secretory vesicles, we sought to determine if this is also the case for ICA69 and whether this protein participates in the process of neuroendocrine secretion. Western blot analysis of ICA69 tissue distribution in the mouse revealed a correlation between expression levels and secretory activity, with the highest expression levels in brain, pancreas, and stomach mucosa. Subcellular fractionation of mouse brain revealed that although most of the ICA69 pool is cytosolic and soluble, a subpopulation is membrane-bound and coenriched with synaptic vesicles. We used immunostaining in the HIT insulin-secreting β-cell line to show that ICA69 localizes in a punctate manner distinct from the insulin granules, suggesting an association with the synaptic-like microvesicles found in these cells. To pursue functional studies on ICA69, we chose to use the model organism Caenorhabditis elegans, for which a homologue of ICA69 exists. We show that the promoter of the C. elegans ICA69 homologue is specifically expressed in all neurons and specialized secretory cells. A deletion mutant was isolated and found to exhibit resistance to the drug aldicarb (an inhibitor of acetylcholinesterase), suggesting defective neurotransmitter secretion in the mutant. On the basis of the aldicarb resistance phenotype, we named the gene ric-19 (resistance to inhibitors of cholinesterase-19). The resistance to aldicarb was rescued by introducing a ric-19 transgene into theric-19 mutant background. This is the first study aimed at dissecting ICA69 function, and our results are consistent with the interpretation that ICA69/RIC-19 is an evolutionarily conserved cytosolic protein participating in the process of neuroendocrine secretion via association with certain secretory vesicles.

scholarly journals New Role for DCR-1/Dicer in Caenorhabditis elegans Innate Immunity against the Highly Virulent Bacterium Bacillus thuringiensis DB27

2013 ◽  
Vol 81 (10) ◽  
pp. 3942-3957 ◽  
Author(s):  
Igor Iatsenko ◽  
Amit Sinha ◽  
Christian Rödelsperger ◽  
Ralf J. Sommer
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Bacillus Thuringiensis ◽  
Defense Mechanisms ◽  
Content Type ◽  
Mirna Processing ◽  
C Elegans ◽  
Nuclear Autoantigenic Sperm Protein ◽  
Bacterium Bacillus ◽  
Underlying Mechanisms

ABSTRACTBacillus thuringiensisproduces toxins that target invertebrates, includingCaenorhabditis elegans. Virulence ofBacillusstrains is often highly specific, such thatB. thuringiensisstrain DB27 is highly pathogenic toC. elegansbut shows no virulence for another model nematode,Pristionchus pacificus. To uncover the underlying mechanisms of the differential responses of the two nematodes toB. thuringiensisDB27 and to reveal theC. elegansdefense mechanisms against this pathogen, we conducted a genetic screen forC. elegansmutants resistant toB. thuringiensisDB27. Here, we describe aB. thuringiensisDB27-resistantC. elegansmutant that is identical tonasp-1, which encodes theC. eleganshomolog of the nuclear-autoantigenic-sperm protein. Gene expression analysis indicated a substantial overlap between the genes downregulated in thenasp-1mutant and targets ofC. elegansdcr-1/Dicer, suggesting thatdcr-1is repressed innasp-1mutants, which was confirmed by quantitative PCR. Consistent with this, thenasp-1mutant exhibits RNA interference (RNAi) deficiency and reduced longevity similar to those of adcr-1mutant. Building on these surprising findings, we further explored a potential role fordcr-1inC. elegansinnate immunity. We show thatdcr-1mutant alleles deficient in microRNA (miRNA) processing, but not those deficient only in RNAi, are resistant toB. thuringiensisDB27. Furthermore,dcr-1overexpression rescues thenasp-1mutant's resistance, suggesting that repression ofdcr-1determines thenasp-1mutant's resistance. Additionally, we identified the collagen-encoding genecol-92as one of the downstream effectors ofnasp-1that play an important role in resistance to DB27. Taken together, these results uncover a previously unknown role for DCR-1/Dicer inC. elegansantibacterial immunity that is largely associated with miRNA processing.

scholarly journals Host immunity alters successional ecology and stability of the microbiome in a C. elegans model

2020 ◽  
Author(s):  
Megan Taylor ◽  
NM Vega
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Community Composition ◽  
Species Interactions ◽  
Host Immunity ◽  
Ecological Processes ◽  
Microbiome Composition ◽  
C Elegans ◽  
Insulin Growth Factor ◽  
A Minor

AbstractA growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation - and the consequences for the ecology of these communities – remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affects the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans. Mutants in innate immunity, in particular the DAF-2/Insulin Growth Factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild type nematodes. We analyze the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and conclude that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We test this hypothesis by introducing a minor perturbation to the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of inter-species interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.ImportanceHere we use a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

scholarly journals Host Immunity Alters Community Ecology and Stability of the Microbiome in a Caenorhabditis elegans Model

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Megan Taylor ◽  
N. M. Vega
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Community Ecology ◽  
Community Composition ◽  
Host Immunity ◽  
Interspecies Interactions ◽  
Ecological Processes ◽  
Content Type ◽  
Microbiome Composition ◽  
Insulin Growth Factor

ABSTRACT A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation—and the consequences for the ecology of these communities—remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affect the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here, we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans. Mutants in innate immunity, in particular the DAF-2/insulin growth factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild-type nematodes. We analyzed the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and concluded that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We tested this hypothesis by introducing a minor perturbation into the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of interspecies interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology. IMPORTANCE Here, we used a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of the host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

scholarly journals Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

2021 ◽  
pp. 1-9
Author(s):  
Dayana Torres Valladares ◽  
Sirisha Kudumala ◽  
Murad Hossain ◽  
Lucia Carvelli
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Genetic Model ◽  
In Vivo Model ◽  
C Elegans ◽  
Hyperactivity Disorder ◽  
In Vitro Data

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in <i>Caenorhabditis elegans</i> to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that <i>C. elegans</i> is a suitable system to study tolerance to drugs of abuse such as amphetamines.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

scholarly journals Stochastic left–right neuronal asymmetry in Caenorhabditis elegans

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150407 ◽  
Author(s):  
Amel Alqadah ◽  
Yi-Wen Hsieh ◽  
Rui Xiong ◽  
Chiou-Fen Chuang
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Calcium Signalling ◽  
Model Organism ◽  
Brain Asymmetry ◽  
C Elegans ◽  
Left And Right ◽  
Left Right Asymmetry ◽  
Neuronal Asymmetry

Left–right asymmetry in the nervous system is observed across species. Defects in left–right cerebral asymmetry are linked to several neurological diseases, but the molecular mechanisms underlying brain asymmetry in vertebrates are still not very well understood. The Caenorhabditis elegans left and right amphid wing ‘C’ (AWC) olfactory neurons communicate through intercellular calcium signalling in a transient embryonic gap junction neural network to specify two asymmetric subtypes, AWC OFF (default) and AWC ON (induced), in a stochastic manner. Here, we highlight the molecular mechanisms that establish and maintain stochastic AWC asymmetry. As the components of the AWC asymmetry pathway are highly conserved, insights from the model organism C. elegans may provide a window onto how brain asymmetry develops in humans. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Hongbing Jiang ◽  
Kevin Chen ◽  
Luis E. Sandoval ◽  
Christian Leung ◽  
David Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Tyrosine Kinase ◽  
Model Organism ◽  
Wiskott Aldrich Syndrome ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Orsay Virus ◽  
Syndrome Protein

ABSTRACT Many fundamental biological discoveries have been made in Caenorhabditis elegans. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in C. elegans. A targeted RNA interference (RNAi) knockdown screen further identified the C. elegans gene nck-1, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in C. elegans identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.

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