Caenorhabditis elegans, a Model Organism for Investigating Immunity

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.

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Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Journal of Virology ◽

10.1128/jvi.00509-17 ◽

2017 ◽

Vol 91 (23) ◽

Cited By ~ 10

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.

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

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.00146-20 ◽

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.

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Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

Anesthesiology ◽

10.1097/00000542-199610000-00027 ◽

1996 ◽

Vol 85 (4) ◽

pp. 901-912 ◽

Cited By ~ 38

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.

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Assessing Host-Virus Codivergence for Close Relatives of Merkel Cell Polyomavirus Infecting African Great Apes

Journal of Virology ◽

10.1128/jvi.00247-16 ◽

2016 ◽

Vol 90 (19) ◽

pp. 8531-8541 ◽

Cited By ~ 13

Author(s):

Nadège F. Madinda ◽

Bernhard Ehlers ◽

Joel O. Wertheim ◽

Chantal Akoua-Koffi ◽

Richard A. Bergl ◽

...

Keyword(s):

Genetic Diversity ◽

Host Specificity ◽

Viral Evolution ◽

Great Apes ◽

Merkel Cell Polyomavirus ◽

Merkel Cell ◽

Human Pathogens ◽

Content Type ◽

Animal Hosts ◽

African Great Apes

ABSTRACTIt has long been hypothesized that polyomaviruses (PyV; familyPolyomaviridae) codiverged with their animal hosts. In contrast, recent analyses suggested that codivergence may only marginally influence the evolution of PyV. We reassess this question by focusing on a single lineage of PyV infecting hominine hosts, the Merkel cell polyomavirus (MCPyV) lineage. By characterizing the genetic diversity of these viruses in seven African great ape taxa, we show that they exhibit very strong host specificity. Reconciliation analyses identify more codivergence than noncodivergence events. In addition, we find that a number of host and PyV divergence events are synchronous. Collectively, our results support codivergence as the dominant process at play during the evolution of the MCPyV lineage. More generally, our results add to the growing body of evidence suggesting an ancient and stable association of PyV and their animal hosts.IMPORTANCEThe processes involved in viral evolution and the interaction of viruses with their hosts are of great scientific interest and public health relevance. It has long been thought that the genetic diversity of double-stranded DNA viruses was generated over long periods of time, similar to typical host evolutionary timescales. This was also hypothesized for polyomaviruses (familyPolyomaviridae), a group comprising several human pathogens, but this remains a point of controversy. Here, we investigate this question by focusing on a single lineage of polyomaviruses that infect both humans and their closest relatives, the African great apes. We show that these viruses exhibit considerable host specificity and that their evolution largely mirrors that of their hosts, suggesting that codivergence with their hosts played a major role in their diversification. Our results provide statistical evidence in favor of an association of polyomaviruses and their hosts over millions of years.

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Stochastic left–right neuronal asymmetry in Caenorhabditis elegans

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0407 ◽

2016 ◽

Vol 371 (1710) ◽

pp. 20150407 ◽

Cited By ~ 16

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’.

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

mBio ◽

10.1128/mbio.00940-17 ◽

2017 ◽

Vol 8 (5) ◽

Cited By ~ 13

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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Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging

Microbiology Spectrum ◽

10.1128/spectrum.00498-21 ◽

2021 ◽

Author(s):

Joshua D. Brycki ◽

Jeremy R. Chen See ◽

Gillian R. Letson ◽

Cade S. Emlet ◽

Lavinia V. Unverdorben ◽

...

Keyword(s):

Gene Expression ◽

Escherichia Coli ◽

Caenorhabditis Elegans ◽

Life Span ◽

Wild Type ◽

Health Span ◽

Content Type ◽

C Elegans ◽

Evolutionarily Conserved

Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans , including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans .

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Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism-associated gene

Human Molecular Genetics ◽

10.1093/hmg/ddaa232 ◽

2020 ◽

Author(s):

Helena Rawsthorne ◽

Fernando Calahorro ◽

Emily Feist ◽

Lindy Holden-Dye ◽

Vincent O’Connor ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Genetic Variants ◽

Social Behaviour ◽

Animal Studies ◽

Model Organism ◽

Autism Spectrum ◽

C Elegans ◽

Important Regulator ◽

Human Mutation ◽

The Impact

Abstract Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism, there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, Caenorhabditis elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms, it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilize this social behaviour to investigate the effect of autism-associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight into complex social behaviour.

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Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis, and Candida bracarensis Virulence and Antifungal Efficacy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00824-20 ◽

2020 ◽

Vol 64 (10) ◽

Author(s):

Ainara Hernando-Ortiz ◽

Estibaliz Mateo ◽

Marcelo Ortega-Riveros ◽

Iker De-la-Pinta ◽

Guillermo Quindós ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Candida Glabrata ◽

Model System ◽

Antifungal Drugs ◽

Phenotypic Traits ◽

Content Type ◽

C Elegans ◽

Host Fungus ◽

Candida Bracarensis ◽

Candida Nivariensis

ABSTRACT Although Candida albicans remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of Candida nivariensis and Candida bracarensis can be misidentified and are underdiagnosed due to phenotypic traits shared with C. glabrata. Little is known about the two cryptic species. Therefore, pathogenesis studies are needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of Caenorhabditis elegans to different Candida species makes this nematode an excellent model for assessing host-fungus interactions. We evaluated the usefulness of C. elegans as a nonconventional host model to analyze the virulence of C. glabrata, C. nivariensis, and C. bracarensis. The three species caused candidiasis, and the highest virulence of C. glabrata was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the C. elegans model. Amphotericin B and azoles showed the highest activity against C. glabrata and C. bracarensis infections, while echinocandins were more active for treating those caused by C. nivariensis. C. elegans proved to be a useful model system for assessing the pathogenicity of these closely related species.

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Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

Molecules ◽

10.3390/molecules25143194 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3194

Author(s):

Begoña Ayuda-Durán ◽

Susana González-Manzano ◽

Ana M. González-Paramás ◽

Celestino Santos-Buelga

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Model Organism ◽

Lipid Peroxides ◽

Biological Research ◽

Loss Of Function ◽

Fluorescent Reporters ◽

C Elegans ◽

High Degree

The nematode Caenorhabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

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