scholarly journals The Pseudomonas aeruginosa accessory genome elements influence virulence towards Caenorhabditis elegans

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Alejandro Vasquez-Rifo ◽  
Isana Veksler-Lublinsky ◽  
Zhenyu Cheng ◽  
Frederick M. Ausubel ◽  
Victor Ambros
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Mobile Element ◽  
Immune Defense ◽  
Virulence Determinants ◽  
Predator Prey ◽  
Accessory Genome ◽  
C Elegans ◽  
Host Pathogen ◽  
Natural Isolates

Abstract Background Multicellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship between Pseudomonas aeruginosa and the nematode Caenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability in P. aeruginosa virulence towards C. elegans to provide evolutionary insights into host-pathogen relationships. Results Natural isolates of P. aeruginosa that exhibit diverse genomes display a broad range of virulence towards C. elegans. Using gene association and genetic analysis, we identify accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we find a viral-like mobile element, the teg block, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence while the presence of CRISPR-Cas associates with higher virulence. Conclusions Our analysis demonstrates substantial strain variation in P. aeruginosa virulence, mediated by specific accessory genome elements that promote increased or decreased virulence. We exemplify that viral-like accessory genome elements that decrease virulence can be restricted by bacterial CRISPR-Cas immune defense systems, and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in virulence maintenance.

scholarly journals ThePseudomonas aeruginosaaccessory genome elements influence virulence towardsCaenorhabditis elegans

2019 ◽  
Author(s):  
Alejandro Vasquez-Rifo ◽  
Isana Veksler-Lublinsky ◽  
Zhenyu Cheng ◽  
Frederick M. Ausubel ◽  
Victor Ambros
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genetic Analysis ◽  
Genetic Basis ◽  
Mobile Element ◽  
The Novel ◽  
Virulence Determinants ◽  
Predator Prey ◽  
Accessory Genome ◽  
C Elegans ◽  
Natural Isolates

ABSTRACTMulticellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship betweenPseudomonas aeruginosaand the nematodeCaenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability inP. aeruginosavirulence towardsC. elegans. Natural isolates ofP. aeruginosathat exhibit diverse genomes display a broad range of virulence towardsC. elegans. Using gene association and genetic analysis, we identified accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we found a viral-like mobile element, thetegblock, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in the restriction of accessory genome elements that may be detrimental to virulence.

scholarly journals bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans

2010 ◽  
Vol 107 (5) ◽  
pp. 2153-2158 ◽  
Author(s):  
Kathleen A. Estes ◽  
Tiffany L. Dunbar ◽  
Jennifer R. Powell ◽  
Frederick M. Ausubel ◽  
Emily R. Troemel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Bacterial Pathogen ◽  
Early Response ◽  
Bzip Transcription Factor ◽  
Wild Type ◽  
Response Gene ◽  
C Elegans ◽  
Infection Response

Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen.

scholarly journals Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model

2009 ◽  
Vol 8 (11) ◽  
pp. 1750-1758 ◽  
Author(s):  
Read Pukkila-Worley ◽  
Anton Y. Peleg ◽  
Emmanouil Tampakakis ◽  
Eleftherios Mylonakis
Keyword(s):  
Candida Albicans ◽  
Caenorhabditis Elegans ◽  
Debaryomyces Hansenii ◽  
Yeast Cells ◽  
Infection Model ◽  
Virulence Determinants ◽  
Tissue Destruction ◽  
C Elegans ◽  
Hyphal Formation

ABSTRACT Candida albicans colonizes the human gastrointestinal tract and can cause life-threatening systemic infection in susceptible hosts. We study here C. albicans virulence determinants using the nematode Caenorhabditis elegans in a pathogenesis system that models candidiasis. The yeast form of C. albicans is ingested into the C. elegans digestive tract. In liquid media, the yeast cells then undergo morphological change to form hyphae, which results in aggressive tissue destruction and death of the nematode. Several lines of evidence demonstrate that hyphal formation is critical for C. albicans pathogenesis in C. elegans. First, two yeast species unable to form hyphae (Debaryomyces hansenii and Candida lusitaniae) were less virulent than C. albicans in the C. elegans assay. Second, three C. albicans mutant strains compromised in their ability to form hyphae (efg1Δ/efg1Δ, flo8Δ/flo8Δ, and cph1Δ/cph1Δ efg1Δ/efg1Δ) were dramatically attenuated for virulence. Third, the conditional tet-NRG1 strain, which enables the external manipulation of morphogenesis in vivo, was more virulent toward C. elegans when the assay was conducted under conditions that permit hyphal growth. Finally, we demonstrate the utility of the C. elegans assay in a screen for C. albicans virulence determinants, which identified several genes important for both hyphal formation in vivo and the killing of C. elegans, including the recently described CAS5 and ADA2 genes. These studies in a C. elegans-C. albicans infection model provide insights into the virulence mechanisms of an important human pathogen.

scholarly journals Feeding behaviour of Caenorhabditis elegans is an indicator of Pseudomonas aeruginosa PAO1 virulence

2014 ◽  
Author(s):  
Shawn Lewenza ◽  
Laetitia Charron-Mazenod ◽  
Lauriane Giroux ◽  
Alexandra D Zamponi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Feeding Behaviour ◽  
Food Sources ◽  
Infection Model ◽  
Bacterial Strains ◽  
Type Iii Effectors ◽  
Type Iii ◽  
C Elegans ◽  
Transposon Mutants

Caenorhabditis elegans is commonly used as an infection model for pathogenesis studies in Pseudomonas aeruginosa. While the standard virulence assays rely on the slow and fast killing or paralysis of nematodes, here we developed a behaviour assay to monitor the preferred bacterial food sources of C. elegans. The type III secretion system is a well-conserved virulence trait that is not required for slow or fast killing of C. elegans. However, ΔexsE mutants that are competent for hypersecretion of ExoS, ExoT and ExoY effectors were avoided as food sources in binary assays. Conversely, mutants lacking the secretion machinery or type III effectors were preferred food sources for PAO1. In binary feeding assays, both food sources were ingested and observed in the gastrointestinal tract, but non-preferred food sources were ultimately avoided. Next we developed a high throughput feeding behaviour assay to test a library of 2370 transposon mutants in order to identify preferred food sources. After primary and secondary screens, 37 mutants were identified as preferred food sources, which included mutations in many known virulence genes and that showed reduced virulence in the slow killing assay. We propose that C. elegans feeding behaviour can be used as a sensitive indicator of virulence for bacterial strains that have moderate worm killing activity.

scholarly journals Feeding behaviour of Caenorhabditis elegans is an indicator of Pseudomonas aeruginosa PAO1 virulence

2014 ◽  
Author(s):  
Shawn Lewenza ◽  
Laetitia Charron-Mazenod ◽  
Lauriane Giroux ◽  
Alexandra D Zamponi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Feeding Behaviour ◽  
Food Sources ◽  
Infection Model ◽  
Bacterial Strains ◽  
Type Iii Effectors ◽  
Type Iii ◽  
C Elegans ◽  
Transposon Mutants

Caenorhabditis elegans is commonly used as an infection model for pathogenesis studies in Pseudomonas aeruginosa. While the standard virulence assays rely on the slow and fast killing or paralysis of nematodes, here we developed a behaviour assay to monitor the preferred bacterial food sources of C. elegans. The type III secretion system is a well-conserved virulence trait that is not required for slow or fast killing of C. elegans. However, ΔexsE mutants that are competent for hypersecretion of ExoS, ExoT and ExoY effectors were avoided as food sources in binary assays. Conversely, mutants lacking the secretion machinery or type III effectors were preferred food sources for PAO1. In binary feeding assays, both food sources were ingested and observed in the gastrointestinal tract, but non-preferred food sources were ultimately avoided. Next we developed a high throughput feeding behaviour assay to test a library of 2370 transposon mutants in order to identify preferred food sources. After primary and secondary screens, 37 mutants were identified as preferred food sources, which included mutations in many known virulence genes and that showed reduced virulence in the slow killing assay. We propose that C. elegans feeding behaviour can be used as a sensitive indicator of virulence for bacterial strains that have moderate worm killing activity.

scholarly journals Caenorhabditis elegans Senses Bacterial Autoinducers

2006 ◽  
Vol 72 (7) ◽  
pp. 5135-5137 ◽  
Author(s):  
Elmus Beale ◽  
Guigen Li ◽  
Man-Wah Tan ◽  
Kendra P. Rumbaugh
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Homoserine Lactones ◽  
C Elegans ◽  
Acylated Homoserine Lactones

ABSTRACT Pseudomonas aeruginosa uses virulence factors controlled by quorum sensing (QS) to kill Caenorhabditis elegans. Here we show that C. elegans is attracted to the acylated homoserine lactones (AHSLs) that mediate QS in P. aeruginosa. Our data also indicate that C. elegans can distinguish AHSLs and may use them to mediate aversive or attractive learning.

scholarly journals Regulatory changes in two chemoreceptor genes contribute to a Caenorhabditis elegans QTL for foraging behavior

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Joshua S Greene ◽  
May Dobosiewicz ◽  
Rebecca A Butcher ◽  
Patrick T McGrath ◽  
Cornelia I Bargmann
Keyword(s):  
Caenorhabditis Elegans ◽  
Foraging Behavior ◽  
Sensory Neurons ◽  
Exploratory Behavior ◽  
Adaptive Variation ◽  
C Elegans ◽  
Regulatory Changes ◽  
Naturally Occurring ◽  
Genome Wide ◽  
Natural Isolates

Natural isolates of C. elegans differ in their sensitivity to pheromones that inhibit exploratory behavior. Previous studies identified a QTL for pheromone sensitivity that includes alternative alleles of srx-43, a chemoreceptor that inhibits exploration through its activity in ASI sensory neurons. Here we show that the QTL is multigenic and includes alternative alleles of srx-44, a second chemoreceptor gene that modifies pheromone sensitivity. srx-44 either promotes or inhibits exploration depending on its expression in the ASJ or ADL sensory neurons, respectively. Naturally occurring pheromone insensitivity results in part from previously described changes in srx-43 expression levels, and in part from increased srx-44 expression in ASJ, which antagonizes ASI and ADL. Antagonism between the sensory neurons results in cellular epistasis that is reflected in their transcription of insulin genes that regulate exploration. These results and genome-wide evidence suggest that chemoreceptor genes may be preferred sites of adaptive variation in C. elegans.

scholarly journals Caenorhabditis elegans as a Model Host for Staphylococcus aureus Pathogenesis

2003 ◽  
Vol 71 (4) ◽  
pp. 2208-2217 ◽  
Author(s):  
Costi D. Sifri ◽  
Jakob Begun ◽  
Frederick M. Ausubel ◽  
Stephen B. Calderwood
Keyword(s):  
Staphylococcus Aureus ◽  
Caenorhabditis Elegans ◽  
Regulatory System ◽  
P38 Map Kinase ◽  
Virulence Determinants ◽  
Loss Of Function ◽  
C Elegans ◽  
Alpha Hemolysin ◽  
Key Aspects ◽  
Virulence Regulator

ABSTRACT Staphylococcus aureus, an important pathogen of humans and other warm-blooded animals, is also capable of killing the nematode Caenorhabditis elegans. Here, we show that C. elegans organisms that are fed S. aureus die over the course of several days in a process that is correlated with the accumulation of bacteria within the nematode digestive tract. Several S. aureus virulence determinants known or speculated to be important in mammalian pathogenesis, including the quorum-sensing global virulence regulatory system agr and the global virulence regulator sarA, the alternative sigma factor σB, alpha-hemolysin, and V8 serine protease, are required for full pathogenicity in nematodes. In addition, several defined C. elegans mutants were examined for susceptibility to S. aureus infection. Enhanced susceptibility to S. aureus killing was observed with loss-of-function mutations in the C. elegans genes esp-2/sek-1 and esp-8/nsy-1, which encode components of a conserved p38 MAP kinase signaling pathway involved in nematode defense against multiple pathogens. These results suggest that key aspects of S. aureus pathogenesis have been conserved, irrespective of the host, and that specific C. elegans host factors can alter susceptibility to this gram-positive human pathogen.

scholarly journals Omega-3 and -6 fatty acids allocate somatic and germline lipids to ensure fitness during nutrient and oxidative stress in Caenorhabditis elegans

2015 ◽  
Vol 112 (50) ◽  
pp. 15378-15383 ◽  
Author(s):  
Dana A. Lynn ◽  
Hans M. Dalton ◽  
Jessica N. Sowa ◽  
Meng C. Wang ◽  
Alexander A. Soukas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Omega 3 ◽  
Resource Reallocation ◽  
C Elegans ◽  
Omega 6 ◽  
Natural Isolates ◽  
The Cost ◽  
Lipid Stores ◽  
And Oxidative Stress

Animals in nature are continually challenged by periods of feast and famine as resources inevitably fluctuate, and must allocate somatic reserves for reproduction to abate evolutionary pressures. We identify an age-dependent lipid homeostasis pathway in Caenorhabditis elegans that regulates the mobilization of lipids from the soma to the germline, which supports fecundity but at the cost of survival in nutrient-poor and oxidative stress environments. This trade-off is responsive to the levels of dietary carbohydrates and organismal oleic acid and is coupled to activation of the cytoprotective transcription factor SKN-1 in both laboratory-derived and natural isolates of C. elegans. The homeostatic balance of lipid stores between the somatic and germ cells is mediated by arachidonic acid (omega-6) and eicosapentaenoic acid (omega-3) precursors of eicosanoid signaling molecules. Our results describe a mechanism for resource reallocation within intact animals that influences reproductive fitness at the cost of somatic resilience.

scholarly journals The Caenorhabditis elegans ABL-1 Tyrosine Kinase Is Required for Shigella flexneri Pathogenesis

2006 ◽  
Vol 72 (7) ◽  
pp. 5043-5051 ◽  
Author(s):  
Elizabeth A. Burton ◽  
Ann Marie Pendergast ◽  
Alejandro Aballay
Keyword(s):  
Caenorhabditis Elegans ◽  
Tyrosine Kinase ◽  
Diarrheal Disease ◽  
Shigella Flexneri ◽  
Model Organism ◽  
Host Susceptibility ◽  
Virulence Plasmid ◽  
Virulence Determinants ◽  
C Elegans

ABSTRACT Shigellosis is a diarrheal disease caused by the gram-negative bacterium Shigella flexneri. Following ingestion of the bacterium, S. flexneri interferes with innate immunity, establishes an infection within the human colon, and initiates an inflammatory response that results in destruction of the tissue lining the gut. Examination of host cell factors required for S. flexneri pathogenesis in vivo has proven difficult due to limited host susceptibility. Here we report the development of a pathogenesis system that involves the use of Caenorhabditis elegans as a model organism to study S. flexneri virulence determinants and host molecules required for pathogenesis. We show that S. flexneri-mediated killing of C. elegans correlates with bacterial accumulation in the intestinal tract of the animal. The S. flexneri virulence plasmid, which encodes a type III secretory system as well as various virulence determinants crucial for pathogenesis in mammalian systems, was found to be required for maximal C. elegans killing. Additionally, we demonstrate that ABL-1, the C. elegans homolog of the mammalian c-Abl nonreceptor tyrosine kinase ABL1, is required for S. flexneri pathogenesis in nematodes. These data demonstrate the feasibility of using C. elegans to study S. flexneri pathogenesis in vivo and provide insight into host factors that contribute to S. flexneri pathogenesis.

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