scholarly journals A novel virulence phenotype rapidly assesses Candida fungal pathogenesis in healthy and immunocompromised Caenorhabditis elegans hosts

2018 ◽  
Author(s):  
Dorian J. Feistel ◽  
Rema Elmostafa ◽  
Nancy Nguyen ◽  
McKenna Penley ◽  
Levi Morran ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Fungal Infection ◽  
Immune Function ◽  
Fungal Infections ◽  
Immunocompromised Host ◽  
Opportunistic Pathogen ◽  
C Elegans ◽  
Pathogen Virulence ◽  
Delayed Reproduction ◽  
Growth Assay

AbstractThe yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human mycobiome and implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.

scholarly journals A Novel Virulence Phenotype Rapidly AssessesCandidaFungal Pathogenesis in Healthy and ImmunocompromisedCaenorhabditis elegansHosts

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Dorian J. Feistel ◽  
Rema Elmostafa ◽  
Nancy Nguyen ◽  
McKenna Penley ◽  
Levi Morran ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Immune Function ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Opportunistic Pathogens ◽  
Pathogenic Potential ◽  
Content Type ◽  
Host Fitness ◽  
Pathogen Virulence ◽  
Delayed Reproduction

ABSTRACTThe yeastCandida albicansis an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. WhileC. albicansis the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicansCandidaspecies are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematodeCaenorhabditis elegansas a perspicuous and efficient model host system to study fungal infections ofCandidapathogens. We find that, in addition to reducing lifetime host survival, exposure toC. albicansresults in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence inC. eleganshosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicansCandidaspecies. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.IMPORTANCEOpportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found thatCandidaspecies, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.

scholarly journals Caenorhabditis elegans as an Infection Model for Pathogenic Mold and Dimorphic Fungi: Applications and Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Chukwuemeka Samson Ahamefule ◽  
Blessing C. Ezeuduji ◽  
James C. Ogbonna ◽  
Anene N. Moneke ◽  
Anthony C. Ike ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Filamentous Fungi ◽  
Virulence Factors ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Infection Model ◽  
Dimorphic Fungi ◽  
C Elegans

The threat burden from pathogenic fungi is universal and increasing with alarming high mortality and morbidity rates from invasive fungal infections. Understanding the virulence factors of these fungi, screening effective antifungal agents and exploring appropriate treatment approaches in in vivo modeling organisms are vital research projects for controlling mycoses. Caenorhabditis elegans has been proven to be a valuable tool in studies of most clinically relevant dimorphic fungi, helping to identify a number of virulence factors and immune-regulators and screen effective antifungal agents without cytotoxic effects. However, little has been achieved and reported with regard to pathogenic filamentous fungi (molds) in the nematode model. In this review, we have summarized the enormous breakthrough of applying a C. elegans infection model for dimorphic fungi studies and the very few reports for filamentous fungi. We have also identified and discussed the challenges in C. elegans-mold modeling applications as well as the possible approaches to conquer these challenges from our practical knowledge in C. elegans-Aspergillus fumigatus model.

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 Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity

2019 ◽  
Author(s):  
Wan-Ting Lee ◽  
Boon-Khai Tan ◽  
Su-Anne Eng ◽  
Gan Chee Yuen ◽  
Kit Lam Chan ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Virulence Factors ◽  
Black Sea ◽  
Sea Cucumber ◽  
Indole Alkaloid ◽  
Host Immunity ◽  
The Black Sea ◽  
C Elegans ◽  
Pathogen Virulence ◽  
Holothuria Atra

AbstractA strategy to circumvent the problem of multidrug resistant pathogen is consumption of functional food rich in anti-infectives targeting bacterial virulence or host immunity. The black sea cucumber (Holothuria atra) is a tropical marine sea cucumer species traditionally consumed as remedy for many ailments. There is a paucity of knowledge the anti-infectives capacity of H. atra and the underlying mechanisms involved. The objectives of this study were to utilize the Caenorhabditis elegans-P. aeruginosa infection model to assess the anti-infective properties of H. atra. We first showed the capacity of a H. atra extract and fraction in promoting survival of C. elegans during a customarily lethal P. aeruginosa infection. The same chemical entities also attenuate the production of several P. aeruginosa virulence factors and biofilm. Treatment of infected transgenic lys-7::GFP worms with H. atra fraction restored the repressed expression of lys-7, a defense enzyme, indicating improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid and inosine. Collectively, our finding shows that H. atra confers survival advantage in C. elegans against P. aeruginosa infection through inhibition of pathogen virulence and eventually, the restitution of host lys-7 expression.

scholarly journals Does Candida albicans Als5p Amyloid Play a Role in Commensalism in Caenorhabditis elegans?

2013 ◽  
Vol 12 (5) ◽  
pp. 703-711 ◽  
Author(s):  
Michael Bois ◽  
Sean Singh ◽  
Alyssa Samlalsingh ◽  
Peter N. Lipke ◽  
Melissa C. Garcia
Keyword(s):  
Candida Albicans ◽  
Caenorhabditis Elegans ◽  
Opportunistic Pathogen ◽  
Egg Laying ◽  
Single Amino Acid ◽  
Dimorphic Fungus ◽  
Egg Hatching ◽  
Content Type ◽  
C Elegans ◽  
Host Microbe Interactions

ABSTRACTCandida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors, including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates and is upregulated during commensal interactions but is downregulated during activeC. albicansinfections. An amyloid-forming core sequence at residues 325 to 331 is important for Als5p function, because a single-amino-acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence. We evaluated the role of Als5p in host-microbe interactions by usingCaenorhabditis elegansnematodes as a host model and feeding themSaccharomyces cerevisiaeexpressing Als5p on the surface. Als5p-expressing yeast had 8.5- and 3.5-fold-increased intestinal accumulation rates compared to Als5p-nonexpressingS. cerevisiaeor yeast expressing amyloid-deficient Als5pV326N, respectively. Surprisingly, this accumulation delayedS. cerevisiae-induced killing ofC. elegans.The median survival time was nearly twice as long as that of nematodes fed nonexpressing or non-amyloid-forming Als5pV326N-expressingS. cerevisiae. Treatment with the amyloid-inhibiting dye Congo red or repression of Als5p expression abrogated the protective effect of Als5p. Furthermore, Als5p had no effect on oocyte quantity or quality, since nematodes fed either empty vector (EV)- or Als5pV326N-expressingS. cerevisiaehad similar egg-laying and egg-hatching rates. This study is the first, to our knowledge, to show that expression of an amyloid-forming protein can attenuate pathogenicity inC. elegans.

scholarly journals Aspergillus Flavus as a Surprise CNS Space Occupying Lesion in an Immunocompetent Pediatric Patient

2020 ◽  
Author(s):  
Mir Ibrahim Sajid ◽  
Noor Malik ◽  
Samira Shabbir Balouch ◽  
Ehsan Bari
Keyword(s):  
Fungal Infection ◽  
Aspergillus Flavus ◽  
Fungal Infections ◽  
Granulomatous Inflammation ◽  
Immunocompromised Host ◽  
Rapid Onset ◽  
Primary Concern ◽  
Left Frontal Lobe ◽  
Onset Condition ◽  
Space Occupying Lesion

Abstract Background: Fungal infections of the CNS are almost always a clinical surprise. Aspergillus species although ubiquitous are more frequently observed in immuno-compromised individuals, upon inhalation of conidia. Most of the fungal infections which happen in humans are opportunistic- in an immunocompromised host. However, we report the case of CNS fungal infection in a healthy child, without any co-morbidities, trauma, or medico-surgical intervention- which could have been the nidus of infection. Case Presentation: We present the case of a 14 year old boy who presented to our institute’s emergency department with primary concern of right sided body hemiparesis since twenty-four hours. This was a rapid-onset condition which was associated with gait disturbances and multiple episodes of vomiting. An MRI of the head showed encapsulated Space Occupying Lesion in the left frontal lobe with surrounding edema. The patient was planned for craniotomy to remove the intracerebral abscess. Histopathology report revealed presence of chronic granulomatous inflammation with necrosis and numerous septate hyphae. A fungus culture was run which confirmed presence of heavy colonies of Aspergillus Flavus. Post-operatively the patient was kept on Voricoazole and anti-inflammatory medications. Conclusion: Fungal infections of the central nervous system are almost always a clinical surprise, and have subtle presentation. Any suspected lesion once removed should be sent for biopsy to rule out the presence of any fungal infection.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis

2008 ◽  
Vol 19 (5) ◽  
pp. 2154-2168 ◽  
Author(s):  
Corey L. Williams ◽  
Marlene E. Winkelbauer ◽  
Jenny C. Schafer ◽  
Edward J. Michaud ◽  
Bradley K. Yoder
Keyword(s):  
Caenorhabditis Elegans ◽  
Joubert Syndrome ◽  
Cystic Kidney ◽  
Basal Bodies ◽  
The Novel ◽  
C Elegans ◽  
Human Genes ◽  
Cilia Formation ◽  
Strong Candidate ◽  
Candidate Loci

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

scholarly journals Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 571-580 ◽  
Author(s):  
William B Raich ◽  
Celine Moorman ◽  
Clay O Lacefield ◽  
Jonah Lehrer ◽  
Dusan Bartsch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Caenorhabditis Elegans ◽  
Trisomy 21 ◽  
Gene Dosage ◽  
Inducible Promoters ◽  
C Elegans ◽  
Dual Specificity ◽  
Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

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