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 Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

2012 ◽  
Vol 81 (2) ◽  
pp. 514-520 ◽  
Author(s):  
Sirena Montalvo-Katz ◽  
Hao Huang ◽  
Michael David Appel ◽  
Maureen Berg ◽  
Michael Shapira
Keyword(s):  
Caenorhabditis Elegans ◽  
Mapk Pathway ◽  
16S Rrna Gene Sequencing ◽  
Egg Laying ◽  
Rrna Gene ◽  
Content Type ◽  
Immune Genes ◽  
C Elegans ◽  
Enhanced Resistance ◽  
Infection Resistance

ABSTRACTThe importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we usedCaenorhabditis elegansto investigate such mechanisms. Since very little is known about the microbes interacting withC. elegansin its natural environment, we began by taking the first steps to characterize theC. elegansmicrobiota. We established a natural-like environment in which initially germfree, wild-type larvae were grown on enriched soil. Bacterial members of the adultC. elegansmicrobiota were isolated by culture and identified using 16S rRNA gene sequencing. Using pure cultures of bacterial isolates as food, we identified two,Bacillus megateriumandPseudomonas mendocina, that enhanced resistance to a subsequent infection with the Gram-negative pathogenPseudomonas aeruginosa. Whereas protection byB. megateriumwas linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred byP. mendocinadepended on weak induction of immune genes regulated by the p38 MAPK pathway. Disruption of the p38 ortholog,pmk-1, abolished protection.P. mendocinaenhanced resistance toP. aeruginosabut not to the Gram-positive pathogenEnterococcus faecalis. Furthermore, protection fromP. aeruginosawas similarly induced by aP. aeruginosagacAmutant with attenuated virulence but not by a differentC. elegans-associatedPseudomonassp. isolate. Our results support a pivotal role for the conserved p38 pathway in microbiota-initiated immune protection and suggest that similarity between microbiota members and pathogens may play a role in such protection.

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

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 .

scholarly journals A Novel Function for Hog1 Stress-Activated Protein Kinase in Controlling White-Opaque Switching and Mating in Candida albicans

2014 ◽  
Vol 13 (12) ◽  
pp. 1557-1566 ◽  
Author(s):  
Shen-Huan Liang ◽  
Jen-Hua Cheng ◽  
Fu-Sheng Deng ◽  
Pei-An Tsai ◽  
Ching-Hsuan Lin
Keyword(s):  
Candida Albicans ◽  
Protein Kinase ◽  
Synthetic Medium ◽  
Opportunistic Pathogen ◽  
Phenotypic Switch ◽  
Content Type ◽  
Host Interactions ◽  
Main Pathway ◽  
Phenotypic Transition ◽  
External Stimuli

ABSTRACTCandida albicansis a commensal in heathy people but has the potential to become an opportunistic pathogen and is responsible for half of all clinical infections in immunocompromised patients. Central to understandingC. albicansbehavior is the white-opaque phenotypic switch, in which cells can undergo an epigenetic transition between the white state and the opaque state. The phenotypic switch regulates multiple properties, including biofilm formation, virulence, mating, and fungus-host interactions. Switching between the white and opaque states is associated with many external stimuli, such as oxidative stress, pH, andN-acetylglucosamine, and is directly regulated by the Wor1 transcriptional circuit. The Hog1 stress-activated protein kinase (SAPK) pathway is recognized as the main pathway for adapting to environmental stress inC. albicans. In this work, we first show that loss of theHOG1gene ina/aand α/α cells, but nota/α cells, results in 100% white-to-opaque switching when cells are grown on synthetic medium, indicating that switching is repressed by thea1/α2 heterodimer that repressesWOR1gene expression. Indeed, switching in thehog1Δ strain was dependent on the presence ofWOR1, as ahog1Δwor1Δ strain did not show switching to the opaque state. Deletion ofPBS2andSSK2also resulted inC. albicanscells switching from white to opaque with 100% efficiency, indicating that the entire Hog1 SAPK pathway is involved in regulating this unique phenotypic transition. Interestingly, all Hog1 pathway mutants also caused defects in shmoo formation and mating efficiencies. Overall, this work reveals a novel role for the Hog1 SAPK pathway in regulating white-opaque switching and sexual behavior inC. albicans.

scholarly journals Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

2004 ◽  
Vol 9 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Brenda R. Ellerbrock ◽  
Eileen M. Coscarelli ◽  
Mark E. Gurney ◽  
Timothy G. Geary
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Screening Method ◽  
Genetic System ◽  
Body Cavity ◽  
Egg Laying ◽  
The Body ◽  
Loss Of Function ◽  
C Elegans ◽  
Automated Method

Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer s disease. Loss-of-function mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semi-automated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient ( egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36K+ channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanism-based discovery of drugs for Alzheimer s disease. ( Journal of Biomolecular Screening 2004:147-152)

A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 797-803 ◽  
Author(s):  
M.J. Stern ◽  
H.R. Horvitz
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Premature Termination ◽  
Cell Interaction ◽  
Egg Laying ◽  
Wild Type ◽  
Mesodermal Cell ◽  
C Elegans ◽  
Somatic Gonad ◽  
Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

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

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.

Effect of structurally related flavonoids from Zuccagnia punctata Cav. on Caenorhabditis elegans

2014 ◽  
Vol 60 (1) ◽  
Author(s):  
Romina E. D’Almeida ◽  
María R. Alberto ◽  
Phillip Morgan ◽  
Margaret Sedensky ◽  
María I. Isla
Keyword(s):  
Caenorhabditis Elegans ◽  
Larval Development ◽  
Free Living ◽  
Egg Hatching ◽  
C Elegans ◽  
Therapeutic Drugs ◽  
Aerial Parts ◽  
Free Living Nematode ◽  
Development Processes ◽  
Anthelmintic Effect

AbstractZuccagnia punctata Cav. (Fabaceae), commonly called jarilla macho or pus-pus, is being used in traditional medicine as an antiseptic, anti-inflammatory and to relieve muscle and bone pain. The aim of this work was to study the anthelmintic effects of three structurally related flavonoids present in aerial parts of Z. punctata Cav. The biological activity of the flavonoids 7-hydroxyflavanone (HF), 3,7-dihydroxyflavone (DHF) and 2´,4´-dihydroxychalcone (DHC) was examined in the free-living nematode Caenorhabditis elegans. Our results showed that among the assayed flavonoids, only DHC showed an anthelmintic effect and alteration of egg hatching and larval development processes in C. elegans. DHC was able to kill 50% of adult nematodes at a concentration of 17 μg/mL. The effect on larval development was observed after 48 h in the presence of 25 and 50 μg/mL DHC, where 33.4 and 73.4% of nematodes remained in the L3 stage or younger. New therapeutic drugs with good efficacy against drug-resistant nematodes are urgently needed. Therefore, DHC, a natural compound present in Z. punctata, is proposed as a potential anthelmintic drug.

scholarly journals Identification of a Cell Death Pathway in Candida albicans during the Response to Pheromone

2010 ◽  
Vol 9 (11) ◽  
pp. 1690-1701 ◽  
Author(s):  
Kevin Alby ◽  
Dana Schaefer ◽  
Racquel Kim Sherwood ◽  
Stephen K. Jones ◽  
Richard J. Bennett
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Laboratory Strain ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Yeast Cells ◽  
Phenotypic Switching ◽  
Morphological Response ◽  
Content Type ◽  
Cell Death Pathway

ABSTRACT Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; both cell types respond to pheromone, but only opaque cells undergo the morphological transition and cell conjugation. We show that approximately 20% of opaque cells, but not white cells, of laboratory strain SC5314 experience pheromone-induced death. Furthermore, analysis of mutant strains revealed that PID was significantly reduced in strains lacking Fig1 or Fus1 transmembrane proteins that are induced during the mating process and, we now show, are necessary for efficient mating in C. albicans. The level of PID was also Ca2+ dependent, as chelation of Ca2+ ions increased cell death to almost 50% of the population. However, in contrast to S. cerevisiae PID, pheromone-induced killing of C. albicans cells was largely independent of signaling via the Ca2+-dependent protein phosphatase calcineurin, even when combined with the loss of Cmk1 and Cmk2 proteins. Finally, we demonstrate that levels of PID vary widely between clinical isolates of C. albicans, with some strains experiencing close to 70% cell death. We discuss these findings in light of the role of prodeath and prosurvival pathways operating in yeast cells undergoing the morphological response to pheromone.

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 Gain-of-Function Mutations inUPC2Are a Frequent Cause ofERG11Upregulation in Azole-Resistant Clinical Isolates of Candida albicans

2012 ◽  
Vol 11 (10) ◽  
pp. 1289-1299 ◽  
Author(s):  
Stephanie A. Flowers ◽  
Katherine S. Barker ◽  
Elizabeth L. Berkow ◽  
Geoffrey Toner ◽  
Sean G. Chadwick ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amino Acid ◽  
Clinical Isolates ◽  
Transcriptional Analysis ◽  
Single Amino Acid ◽  
Ergosterol Biosynthesis ◽  
Amino Acid Substitutions ◽  
Gain Of Function ◽  
Content Type ◽  
Zinc Cluster

ABSTRACTInCandida albicans, Upc2 is a zinc-cluster transcription factor that targets genes, including those of the ergosterol biosynthesis pathway. To date, three documentedUPC2gain-of-function (GOF) mutations have been recovered from fluconazole-resistant clinical isolates that contribute to an increase inERG11expression and decreased fluconazole susceptibility. In a group of 63 isolates with reduced susceptibility to fluconazole, we found that 47 overexpressedERG11by at least 2-fold over the average expression levels in 3 unrelated fluconazole-susceptible strains. Of those 47 isolates, 29 contained a mutation inUPC2, whereas the remaining 18 isolates did not. Among the isolates containing mutations inUPC2, we recovered eight distinct mutations resulting in putative single amino acid substitutions: G648D, G648S, A643T, A643V, Y642F, G304R, A646V, and W478C. Seven of these resulted in increasedERG11expression, increased cellular ergosterol, and decreased susceptibility to fluconazole compared to the results for the wild-type strain. Genome-wide transcriptional analysis was performed for the four strongest Upc2 amino acid substitutions (A643V, G648D, G648S, and Y642F). Genes commonly upregulated by all four mutations included those involved in ergosterol biosynthesis, in oxidoreductase activity, the major facilitator efflux pump encoded by theMDR1gene, and the uncharacterized ATP binding cassette transporterCDR11. These findings demonstrate that gain-of-function mutations inUPC2are more prevalent among clinical isolates than previously thought and make a significant contribution to azole antifungal resistance, but the findings do not account forERG11overexpression in all such isolates ofC. albicans.

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