Faculty Opinions recommendation of Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model.

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.

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Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans

Microorganisms ◽

10.3390/microorganisms9020310 ◽

2021 ◽

Vol 9 (2) ◽

pp. 310

Author(s):

Masayuki Hashimoto ◽

Yi-Fen Ma ◽

Sin-Tian Wang ◽

Chang-Shi Chen ◽

Ching-Hao Teng

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Caenorhabditis Elegans ◽

Large Scale ◽

Iron Acquisition ◽

Infection Model ◽

High Throughput Analysis ◽

E Coli ◽

C Elegans ◽

Tract Infections

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

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A Pathoadaptive Deletion in an Enteroaggregative Escherichia coli Outbreak Strain Enhances Virulence in a Caenorhabditis elegans Model

Infection and Immunity ◽

10.1128/iai.00014-10 ◽

2010 ◽

Vol 78 (9) ◽

pp. 4068-4076 ◽

Cited By ~ 11

Author(s):

Jennifer Hwang ◽

Lisa M. Mattei ◽

Laura G. VanArendonk ◽

Philip M. Meneely ◽

Iruka N. Okeke

Keyword(s):

Escherichia Coli ◽

Caenorhabditis Elegans ◽

Epithelial Cells ◽

Genetic Material ◽

Decarboxylase Activity ◽

Multicopy Plasmid ◽

Lysine Decarboxylase ◽

Outbreak Strain ◽

E Coli ◽

C Elegans

ABSTRACT Enteroaggregative Escherichia coli (EAEC) strains are important diarrheal pathogens. EAEC strains are defined by their characteristic stacked-brick pattern of adherence to epithelial cells but show heterogeneous virulence and have different combinations of adhesin and toxin genes. Pathoadaptive deletions in the lysine decarboxylase (cad) genes have been noted among hypervirulent E. coli subtypes of Shigella and enterohemorrhagic E. coli. To test the hypothesis that cad deletions might account for heterogeneity in EAEC virulence, we developed a Caenorhabditis elegans pathogenesis model. Well-characterized EAEC strains were shown to colonize and kill C. elegans, and differences in virulence could be measured quantitatively. Of 49 EAEC strains screened for lysine decarboxylase activity, 3 tested negative. Most notable is isolate 101-1, which was recovered in Japan, from the largest documented EAEC outbreak. EAEC strain 101-1 was unable to decarboxylate lysine in vitro due to deletions in cadA and cadC, which, respectively, encode lysine decarboxylase and a transcriptional activator of the cadAB genes. Strain 101-1 was significantly more lethal to C. elegans than control strain OP50. Lethality was attenuated when the lysine decarboxylase defect was complemented from a multicopy plasmid and in single copy. In addition, restoring lysine decarboxylase function produced derivatives of 101-1 deficient in aggregative adherence to cultured human epithelial cells. Lysine decarboxylase inactivation is pathoadapative in an important EAEC outbreak strain, and deletion of cad genes could produce hypervirulent EAEC lineages in the future. These results suggest that loss, as well as gain, of genetic material can account for heterogeneous virulence among EAEC strains.

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E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans

10.1101/013029 ◽

2014 ◽

Author(s):

Alper Akay ◽

Peter Sarkies ◽

Eric Alexander Miska

Keyword(s):

Small Rnas ◽

Biological Function ◽

Rapid Development ◽

Rnai Pathway ◽

Regulate Gene Expression ◽

Double Stranded Rna ◽

E Coli ◽

C Elegans ◽

Non Coding Rna ◽

Rnai Response

The discovery of RNA interference (RNAi) in C. elegans has had a major impact on scientific research, led to the rapid development of RNAi tools and has inspired RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the biological function of this mechanism is unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate gene expression in C. elegans when E. coli is offered as food. This was surprising given that C. elegans is unlikely to encounter E. coli in nature. To directly test the hypothesis that the E. coli OxyS non-coding RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs from C. elegans after feeding with bacteria. We clearly demonstrate that the OxyS non-coding RNA does not trigger an RNAi response in C. elegans. We conclude that the biology of environmental RNAi remains to be discovered.

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Conditioning Protects C. elegans from Lethal Effects of Enteropathogenic E. coli by Activating Genes that Regulate Lifespan and Innate Immunity

Cell Host & Microbe ◽

10.1016/j.chom.2009.04.012 ◽

2009 ◽

Vol 5 (5) ◽

pp. 450-462 ◽

Cited By ~ 49

Author(s):

Akwasi Anyanful ◽

Kirk A. Easley ◽

Guy M. Benian ◽

Daniel Kalman

Keyword(s):

Innate Immunity ◽

Lethal Effects ◽

E Coli ◽

C Elegans

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Giardia duodenalis-induced alterations of commensal bacteria killCaenorhabditis elegans: a new model to study microbial-microbial interactions in the gut

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00335.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. G550-G561 ◽

Cited By ~ 31

Author(s):

Teklu K. Gerbaba ◽

Pratyush Gupta ◽

Kevin Rioux ◽

Dave Hansen ◽

Andre G. Buret

Keyword(s):

Bacterial Colonization ◽

Giardia Duodenalis ◽

Microbial Interactions ◽

Commensal Bacteria ◽

In Vivo Model ◽

Functional Changes ◽

E Coli ◽

C Elegans ◽

Human Microbiota

Giardia duodenalis is the most common cause of parasitic diarrhea worldwide and a well-established risk factor for postinfectious irritable bowel syndrome. We hypothesized that Giardia-induced disruptions in host-microbiota interactions may play a role in the pathogenesis of giardiasis and in postgiardiasis disease. Functional changes induced by Giardia in commensal bacteria and the resulting effects on Caenorhabditis elegans were determined. Although Giardia or bacteria alone did not affect worm viability, combining commensal Escherichia coli bacteria with Giardia became lethal to C. elegans. Giardia also induced killing of C. elegans with attenuated Citrobacter rodentium espF and map mutant strains, human microbiota from a healthy donor, and microbiota from inflamed colonic sites of ulcerative colitis patient. In contrast, combinations of Giardia with microbiota from noninflamed sites of the same patient allowed for worm survival. The synergistic lethal effects of Giardia and E. coli required the presence of live bacteria and were associated with the facilitation of bacterial colonization in the C. elegans intestine. Exposure to C. elegans and/or Giardia altered the expression of 172 genes in E. coli. The genes affected by Giardia included hydrogen sulfide biosynthesis (HSB) genes, and deletion of a positive regulator of HSB genes, cysB, was sufficient to kill C. elegans even in the absence of Giardia. Our findings indicate that Giardia induces functional changes in commensal bacteria, possibly making them opportunistic pathogens, and alters host-microbe homeostatic interactions. This report describes the use of a novel in vivo model to assess the toxicity of human microbiota.

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Carbon Nano-Onions as Nontoxic and High-Fluorescence Bioimaging Agent in Food Chain—An In Vivo Study from Unicellular E. coli to Multicellular C. elegans

Materials Express ◽

10.1166/mex.2012.1064 ◽

2012 ◽

Vol 2 (2) ◽

pp. 105-114 ◽

Cited By ~ 63

Author(s):

Sumit Kumar Sonkar ◽

Mitrajit Ghosh ◽

Manas Roy ◽

Ameerunisha Begum ◽

Sabyasachi Sarkar

Keyword(s):

Food Chain ◽

E Coli ◽

C Elegans ◽

Fluorescence Bioimaging ◽

High Fluorescence

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Interplay between mitochondria and diet mediates pathogen and stress resistance inC. elegans

10.1101/154393 ◽

2017 ◽

Author(s):

Alexey V. Revtovich ◽

Ryan Lee ◽

Natalia V. Kirienko

Keyword(s):

Stress Resistance ◽

Vitamin B12 Deficiency ◽

E Coli ◽

C Elegans ◽

Mitochondrial Homeostasis ◽

Physiological Consequence ◽

Organismal Biology ◽

Host Health ◽

B12 Deficiency ◽

Dietary Deficiency

SummaryDiet is a crucial determinant of organismal biology. Here we demonstrate the dramatic impact of a subtle shift in diet on the ability ofCaenorhabditis elegansto survive pathogenic or abiotic stress. Interestingly, this shift occurs independently of canonical host defense pathways, arising instead from improvements in mitochondrial health. Using a variety of assays, we reveal that the most commonC. elegansfood source (E. coliOP50) results in a vitamin B12 deficiency that compromises mitochondrial homeostasis. Increasing B12 supply by feeding onE. coliHT115 or by supplementing bacterial media with methylcobalamin restored mitochondrial function, even if the bacteria were dead. B12 supplementation also efficiently increased host health without adversely affecting lifespan. Our study forges a molecular link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework. The ubiquity of B12 deficiency (~10-40% of US adults) highlights the importance of our findings.

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From pathogen to commensal to probiotic: modification of Microbacterium nematophilum-C. elegans interaction during chronic infection by the absence of host insulin signalling

10.1101/2020.04.01.020933 ◽

2020 ◽

Author(s):

Maria Gravato-Nobre ◽

Jonathan Hodgkin ◽

Petros Ligoxygakis

Keyword(s):

Chronic Infection ◽

Insulin Signalling ◽

Avirulent Strain ◽

Opportunistic Pathogens ◽

E Coli ◽

C Elegans ◽

Intestinal Infections ◽

Age Dependent ◽

Immune Defences ◽

Nematode Worm

ABSTRACTThe nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and health span. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, long-lived daf-2 mutants were resistant to chronic infection, showing reduced colonisation and a higher age-dependent vigour. In fact, UV336 acted as a probiotic in daf-2, showing a lifespan extension beyond OP50, the E. coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Since the DAF-2/DAF-16 axis is present in most metazoans this suggests an evolutionary conserved host mechanism to modify a pathogen to a commensal.

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