scholarly journals Transcriptome analysis of Caenorhabditis elegans lacking heme peroxidase SKPO-1 reveals an altered response to Enterococcus faecalis

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Yi Liu ◽  
Daniel Martinez-Martinez ◽  
Clara L Essmann ◽  
Melissa R Cruz ◽  
Filipe Cabreiro ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Enterococcus Faecalis ◽  
Transcriptome Analysis ◽  
Model Organism ◽  
Force Microscopy ◽  
C Elegans ◽  
Atomic Force ◽  
Genes Encoding ◽  
Heme Peroxidases ◽  
Cuticle Development

Abstract The nematode Caenorhabditis elegans is commonly used as a model organism in studies of the host immune response. The worm encodes twelve peroxidase-cyclooxygenase superfamily members, making it an attractive model in which to study the functions of heme peroxidases. In previous work, loss of one of these peroxidases, SKPO-1 (ShkT-containing peroxidase), rendered C. elegans more sensitive to the human, Gram-positive pathogen Enterococcus faecalis. SKPO-1 was localized to the hypodermis of the animals where it also affected cuticle development as indicated by a morphological phenotype called “dumpy.” In this work, a better understanding of how loss of skpo-1 impacts both sensitivity to pathogen as well as cuticle development was sought by subjecting a deletion mutant of skpo-1 to transcriptome analysis using RNA sequencing following exposure to control (Escherichia coli) and pathogenic (E. faecalis) feeding conditions. Loss of skpo-1 caused a general upregulation of genes encoding collagens and other proteins related to cuticle development. On E. faecalis, these animals also failed to upregulate guanylyl cyclases that are often involved in environmental sensing. Hoechst straining revealed increased permeability of the cuticle and atomic force microscopy exposed the misalignment of the cuticular annuli and furrows. These findings provide a basis for better understanding of the morphological as well as the pathogen sensitivity phenotypes associated with loss of SKPO-1 function.

Molecular characterization of the metabotropic glutamate receptor family in Caenorhabditis elegans

2006 ◽  
Vol 34 (5) ◽  
pp. 942-948 ◽  
Author(s):  
J. Dillon ◽  
N.A. Hopper ◽  
L. Holden-Dye ◽  
V. O'Connor
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Characterization ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Model Organism ◽  
Metabotropic Glutamate ◽  
C Elegans ◽  
Genes Encoding ◽  
G Protein Coupled

mGluRs (metabotropic glutamate receptors) are G-protein-coupled receptors that play an important neuromodulatory role in the brain. Glutamatergic transmission itself plays a fundamental role in the simple nervous system of the model organism Caenorhabditis elegans, but little is known about the contribution made by mGluR signalling. The sequenced genome of C. elegans predicts three distinct genes, mgl-1, mgl-2 and mgl-3 (designated Y4C6A.2). We have used in silico and cDNA analyses to investigate the genes encoding mgls. Our results indicate that mgl genes constitute a gene family made up of three distinct subclasses of receptor. Our transcript analysis highlights potential for complex gene regulation with respect to both expression and splicing. Further, we identify that the predicted proteins encoded by mgls harbour structural motifs that are likely to regulate function. Taken together, this molecular characterization provides a platform to further investigate mGluR function in the model organism C. elegans.

scholarly journals NHR-49 Transcription Factor Regulates Immunometabolic Response and Survival of Caenorhabditis elegans during Enterococcus faecalis Infection

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Madhumanti Dasgupta ◽  
Meghana Shashikanth ◽  
Anjali Gupta ◽  
Anjali Sandhu ◽  
Atreyee De ◽  
...  
Keyword(s):  
Immune Response ◽  
Caenorhabditis Elegans ◽  
Enterococcus Faecalis ◽  
Lipid Synthesis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Content Type ◽  
Immune Effector ◽  
C Elegans ◽  
Genes Encoding

ABSTRACT Immune response to pathogens is energetically expensive to the host; however, the cellular source of energy to fuel immune response remains unknown. In this study, we show that Caenorhabditis elegans exposed to pathogenic Gram-positive and Gram-negative bacteria or yeast rapidly utilizes lipid droplets, the major energy reserve. The nematode’s response to the pathogenic bacterium Enterococcus faecalis entails metabolic rewiring for the upregulation of several genes involved in lipid utilization and downregulation of lipid synthesis genes. Genes encoding acyl-CoA synthetase ACS-2, involved in lipid metabolism, and flavin monooxygenase FMO-2, involved in detoxification, are two highly upregulated genes during E. faecalis infection. We find that both ACS-2 and FMO-2 are necessary for survival and rely on NHR-49, a peroxisome proliferator-activated receptor alpha (PPARα) ortholog, for upregulation during E. faecalis infection. Thus, NHR-49 regulates an immunometabolic axis of survival in C. elegans by modulating breakdown of lipids as well as immune effector production upon E. faecalis exposure.

A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface

Microbiology ◽  
2003 ◽  
Vol 149 (11) ◽  
pp. 3221-3229 ◽  
Author(s):  
G. W. P. Joshua ◽  
A. V. Karlyshev ◽  
M. P. Smith ◽  
K. E. Isherwood ◽  
R. W. Titball ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Biofilm Formation ◽  
Yersinia Pseudotuberculosis ◽  
Model Organism ◽  
Severe Infection ◽  
Evolutionary Divergence ◽  
Control Mechanisms ◽  
C Elegans ◽  
Pathway Gene ◽  
Genes Encoding

To investigate Yersinia pathogenicity and the evolutionary divergence of the genus, the effect of pathogenic yersiniae on the model organism Caenorhabditis elegans was studied. Three strains of Yersinia pestis, including a strain lacking pMT1, caused blockage and death of C. elegans; one strain, lacking the haemin storage (hms) locus, caused no effect. Similarly, 15 strains of Yersinia enterocolitica caused no effect. Strains of Yersinia pseudotuberculosis showed different levels of pathogenicity. The majority of strains (76 %) caused no discernible effect; 5 % caused a weak infection, 9·5 % an intermediate infection, and 9·5 % a severe infection. There was no consistent relationship between serotype and severity of infection; nor was there any relationship between strains causing infection of C. elegans and those able to form a biofilm on an abiotic surface. Electron microscope and cytochemical examination of infected worms indicated that the infection phenotype is a result of biofilm formation on the head of the worm. Seven transposon mutants of Y. pseudotuberculosis strain YPIII pIB1 were completely or partially attenuated; mutated genes included genes encoding proteins involved in haemin storage and lipopolysaccharide biosynthesis. A screen of 15 defined C. elegans mutants identified four where mutation caused (complete) resistance to infection by Y. pseudotuberculosis YPIII pIB1. These mutants, srf-2, srf-3, srf-5 and the dauer pathway gene daf-1, also exhibit altered binding of lectins to the nematode surface. This suggests that biofilm formation on a biotic surface is an interactive process involving both bacterial and invertebrate control mechanisms.

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.

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

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.

scholarly journals Mechanical properties measured by atomic force microscopy define health biomarkers in ageing C. elegans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Clara L. Essmann ◽  
Daniel Martinez-Martinez ◽  
Rosina Pryor ◽  
Kit-Yi Leung ◽  
Kalaivani Bala Krishnan ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Atomic Force Microscopy ◽  
Force Microscopy ◽  
C Elegans ◽  
Atomic Force

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

Molecules ◽  
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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