Lactobacilli in a clade ameliorate age-dependent decline of thermotaxis behavior in Caenorhabditis elegans

AbstractDiet is proposed to affect brain aging. However, the causality and mechanism of dietary effects on brain aging are still unclear due to the long time scales of aging. The nematode Caenorhabditis elegans (C. elegans) has led aging research because of its short lifespan and easy genetic manipulation. When fed the standard laboratory diet, Escherichia coli (E. coli), C. elegans experiences an age-dependent decline in temperature-food associative learning, called thermotaxis. To address if diet ameliorates this decline, we screened 35 different lactic acid bacteria as alternative diets. We found that Lactobacilli in a clade enriched with heterofermentative bacteria ameliorated age-dependent decline. On the other hand, homofermentative Lactobacillus species did not show this beneficial effect. Lactobacilli affected the thermotaxis of aged animals through DAF-16, an ortholog of mammalian FOXO transcription factor, while the effect on the thermotaxis was independent of the lifespan and locomotion. Our results demonstrate that diet can impact brain aging without changing the lifespan and that bacterial screen using C. elegans is a powerful approach to investigate age-dependent behavioral decline.

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

Current Aging Science ◽

10.2174/1874609813999210104203614 ◽

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.

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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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DAF-16 and SMK-1 Contribute to Innate Immunity During Adulthood in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401166 ◽

2020 ◽

Vol 10 (5) ◽

pp. 1521-1539 ◽

Cited By ~ 1

Author(s):

Daniel R. McHugh ◽

Elena Koumis ◽

Paul Jacob ◽

Jennifer Goldfarb ◽

Michelle Schlaubitz-Garcia ◽

...

Keyword(s):

Innate Immunity ◽

Immune System ◽

Caenorhabditis Elegans ◽

Host Defense ◽

Insulin Signaling ◽

Bacterial Pathogens ◽

C Elegans ◽

Link Type ◽

Age Dependent ◽

Over Time

Aging is accompanied by a progressive decline in immune function termed “immunosenescence”. Deficient surveillance coupled with the impaired function of immune cells compromises host defense in older animals. The dynamic activity of regulatory modules that control immunity appears to underlie age-dependent modifications to the immune system. In the roundworm Caenorhabditis elegans levels of PMK-1 p38 MAP kinase diminish over time, reducing the expression of immune effectors that clear bacterial pathogens. Along with the PMK-1 pathway, innate immunity in C. elegans is regulated by the insulin signaling pathway. Here we asked whether DAF-16, a Forkhead box (FOXO) transcription factor whose activity is inhibited by insulin signaling, plays a role in host defense later in life. While in younger C. elegansDAF-16 is inactive unless stimulated by environmental insults, we found that even in the absence of acute stress the transcriptional activity of DAF-16 increases in an age-dependent manner. Beginning in the reproductive phase of adulthood, DAF-16 upregulates a subset of its transcriptional targets, including genes required to kill ingested microbes. Accordingly, DAF-16 has little to no role in larval immunity, but functions specifically during adulthood to confer resistance to bacterial pathogens. We found that DAF-16-mediated immunity in adults requires SMK-1, a regulatory subunit of the PP4 protein phosphatase complex. Our data suggest that as the function of one branch of the innate immune system of C. elegans (PMK-1) declines over time, DAF-16-mediated immunity ramps up to become the predominant means of protecting adults from infection, thus reconfiguring immunity later in life.

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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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DAF-18 is required for the age-dependent increase in DAF-16 activity in Caenorhabditis elegans

10.1101/2020.11.16.384529 ◽

2020 ◽

Author(s):

Kali Carrasco ◽

Matthew J. Youngman

Keyword(s):

Caenorhabditis Elegans ◽

Functional Characterization ◽

Growth Factor Signaling ◽

Dynamic Activity ◽

Post Translational Modifications ◽

C Elegans ◽

Regulatory Module ◽

Phospholipid Signaling ◽

Age Dependent ◽

Foxo Transcription Factors

ABSTRACTThe insulin/insulin-like growth factor signaling (IIS) pathway modulates growth, survival, and lifespan by regulating FOXO transcription factors. In Caenorhabditis elegans, IIS maintains DAF-16/FOXO in an inactive state unless animals are challenged by environmental stress. Recent evidence suggests that DAF-16 becomes activated as part of normal aging in C. elegans, yet the regulatory module responsible for this phenomenon is largely undefined. Embedded within IIS is phospholipid signaling in which PIP3 produced by the PI3 kinase AGE-1 is an upstream event in DAF-16 inhibition. Countering AGE-1 is DAF-18, an ortholog of human PTEN phosphatase that dephosphorylates PIP3. Although it is required for normal lifespan in C. elegans, functional characterization of DAF-18 has primarily focused on its roles during development in the germline and neurons. In this study we asked whether DAF-18 plays a role in the age-dependent activation of DAF-16, and specifically in DAF-16-mediated immunity. Our data show that DAF-18 is expressed in multiple tissues during adulthood. We found that DAF-18 contributes to host defense in adult animals by functioning in the neurons and intestine, likely working through DAF-16 which acts in those same tissues to confer immunity. Supporting this possibility, DAF-18 was required for increased DAF-16 transcriptional activity during aging. Post-translational modifications including ubiquitination and sumoylation appear to be required for the function of DAF-18 during aging in C. elegans, indicating that strategies to modulate PTEN activity are evolutionarily conserved. Our results establish an important role for DAF-18 later in life and imply that it is a critical component of a neuroendocrine signaling circuit that governs the dynamic activity of DAF-16.

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Behavioural phenotyping of C. elegans on UV-killed E. coli mutants v1

10.17504/protocols.io.b2dhqa36 ◽

2021 ◽

Author(s):

Saul Moore

Keyword(s):

Caenorhabditis Elegans ◽

Gene Deletion ◽

Uv Light ◽

Single Gene ◽

Deletion Mutants ◽

E Coli ◽

C Elegans ◽

Behavioural Phenotyping ◽

Keio Collection ◽

Single Gene Deletion

Protocol for screening candidate behaviour-modifying E. coli BW25113 single-gene deletion mutants from the 'Keio Collection', to investigate their effects on Caenorhabditis elegans behaviour when killed by ultraviolet (UV) light

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154 Virulence Potential of Antimicrobial Resistant Extraintestinal Pathogenic Escherichia coli from Poultry in a Caenorhabditis Elegans Model

Journal of Animal Science ◽

10.1093/jas/skab235.151 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 84-84

Author(s):

Chongwu Yang ◽

Moussa Diarra ◽

Muhammad Attiq Rehman ◽

Linyan Li ◽

Hai Yu ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Life Span ◽

Negative Control ◽

Coli Strain ◽

Poultry Meat ◽

Infection Model ◽

E Coli ◽

C Elegans ◽

Virulence Potential ◽

Retail Meats

Abstract This study investigated virulence potential of poultry antimicrobial resistant extraintestinal pathogenic E. coli (ExPEC). A total of 46 E. coli isolates from poultry meat, feces, or humans were sequenced and identified as ExPEC. Based on their characteristics, eight of these ExPEC isolates were evaluated for their potentials using a Caenorhabditis elegans infection model. The life-span of C. elegans in response to these eight isolates was examined in three life-span experiments: 1) E. coli OP 50 (negative control), K88+ enterotoxigenic E. coli strain JG280 (positive control), and an ExPEC isolate from human urinal tract infection; 2) three ExPEC isolates from chicken and turkey retail meats; 3) four ExPEC isolates from chicken feces with different antimicrobial resistance (AMR) profiles or a various number of virulence genes (VGs). All 46 isolates belonged to 24 serotypes among which 6 were of serotype O25:H4 Sequence Type 131 (ST131). Interestingly, all ST 131 isolates from chicken or turkey retail meats clustered with a human UTI isolate belonging to the similar serotype and ST type. The types and numbers of AGRs and VGs varied among the eight selected isolates for C. elegans model. The human ExPEC induced a similar effect as the JG280 on reducing (P < 0.05) survival of C. elegans. Interestingly, chicken and turkey meat ExPEC isolates, caused similar negative impacts on the survival of worms as the human ExPEC. Additionally, fecal ExPEC isolates reduced (P < 0.05) the survival of C. elegans compared to OP50. However, the survival of C. elegans was not reduced with an increasing number of VGs and did not seem to be affected by AMR profiles. This study indicated the virulence potential of ExPEC isolates from retail poultry meat or feces. The relationship between specific AMR profiles and/or numbers of VGs with pathogenicity in these E. coli isolates deserves further investigations.

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Evaluating the Pathogenic Potential of Environmental Escherichia coli by Using the Caenorhabditis elegans Infection Model

Applied and Environmental Microbiology ◽

10.1128/aem.03501-12 ◽

2013 ◽

Vol 79 (7) ◽

pp. 2435-2445 ◽

Cited By ~ 15

Author(s):

Alexandra Merkx-Jacques ◽

Anja Coors ◽

Roland Brousseau ◽

Luke Masson ◽

Alberto Mazza ◽

...

Keyword(s):

Escherichia Coli ◽

Caenorhabditis Elegans ◽

Virulence Genes ◽

Human Health Risk ◽

Environmental Isolates ◽

Pathogenic Potential ◽

Content Type ◽

E Coli ◽

C Elegans ◽

Infection Assay

ABSTRACTThe detection and abundance ofEscherichia coliin water is used to monitor and mandate the quality of drinking and recreational water. Distinguishing commensal waterborneE. coliisolates from those that cause diarrhea or extraintestinal disease in humans is important for quantifying human health risk. A DNA microarray was used to evaluate the distribution of virulence genes in 148E. colienvironmental isolates from a watershed in eastern Ontario, Canada, and in eight clinical isolates. Their pathogenic potential was evaluated withCaenorhabditis elegans, and the concordance between the bioassay result and the pathotype deduced by genotyping was explored. Isolates identified as potentially pathogenic on the basis of their complement of virulence genes were significantly more likely to be pathogenic toC. elegansthan those determined to be potentially nonpathogenic. A number of isolates that were identified as nonpathogenic on the basis of genotyping were pathogenic in the infection assay, suggesting that genotyping did not capture all potentially pathogenic types. The detection of the adhesin-encoding genessfaD,focA, andfocG, which encode adhesins; ofiroN2, which encodes a siderophore receptor; ofpic, which encodes an autotransporter protein; and ofb1432, which encodes a putative transposase, was significantly associated with pathogenicity in the infection assay. Overall,E. coliisolates predicted to be pathogenic on the basis of genotyping were indeed so in theC. elegansinfection assay. Furthermore, the detection ofC. elegans-infective environmental isolates predicted to be nonpathogenic on the basis of genotyping suggests that there are hitherto-unrecognized virulence factors or combinations thereof that are important in the establishment of infection.

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Expression of β-1,4-galactosyltransferases during Aging in Caenorhabditis elegans

Gerontology ◽

10.1159/000510722 ◽

2020 ◽

Vol 66 (6) ◽

pp. 571-581

Author(s):

Jennifer Kremer ◽

Cornelia Brendel ◽

Elisabeth Karin Maria Mack ◽

Hildegard Isolde Dietlinde Mack

Keyword(s):

Caenorhabditis Elegans ◽

Model Organism ◽

Mrna Levels ◽

Germline Stem Cells ◽

Wild Type ◽

Activity Increase ◽

C Elegans ◽

Targeted Analysis ◽

Age Dependent ◽

Plasma Activity

Background: Altered plasma activity of β-1,4-galactosyltransferases (B4GALTs) is a novel candidate biomarker of human aging. B4GALT1 is assumed to be largely responsible for this activity increase, but how it modulates the aging process is unclear at present. Objectives: To determine how expression of B4GALT1 and other B4GALT enzymes changes during aging of an experimentally tractable model organism, Caenorhabditis elegans. Methods: Targeted analysis of mRNA levels of all 3 C. elegans B4GALT family members was performed by qPCR in wild-type and in long-lived daf-2 (insulin/IGF1-like receptor)-deficient or germline-deficient animals. Results: bre-4 (B4GALT1/2/3/4) is the only B4GALT whose expression increases during aging in wild-type worms. In addition, bre-4 levels also rise during aging in long-lived daf-2-deficient worms, but not in animals that are long-lived due to the lack of germline stem cells. On the other hand, expression of sqv-3 (B4GALT7) and of W02B12.11 (B4GALT5/6) appears decreased or constant, respectively, in all backgrounds during aging. Conclusions: The age-dependent bre-4 mRNA increase in C. elegans parallels the age-dependent B4GALT activity increase in humans and is consistent with C. elegans being a suitable experimental organism to define potentially conserved roles of B4GALT1 during aging.

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