Hoang, Hieu D. et al. (2011) International Worm Meeting "Identifying mechanisms critical for sperm guidance to oocytes."

Prasain, J., Miller, Michael A., Edmonds, Johnathan W., Hoang, Hieu D.

[International Worm Meeting, 2011]

Fertilization is dependent upon fusion of sperm and oocyte. The mechanism(s) by which motile sperm find oocytes within the female reproductive tract is not well understood. Our published data provide strong evidence that C. elegans oocytes secrete F-series prostaglandins that guide sperm to the spermatheca (Kubagawa et al., 2006; Edmonds et al., 2010). Prostaglandins (PGs) are lipid hormones that are targets of nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen. Although PG synthesis pathways in mammals have been largely delineated, these pathways in worms are unexplored. The C. elegans genome lacks PG G/H synthase homologs, which catalyze the 1st step in PG synthesis, yet encodes a wide array of predicted PG D, E, and F synthases that act downstream. Our model is that PG synthesis in oocytes initiates by a novel mechanism that generates substrates for conserved PG synthases that in turn generate F-series PG analogs. Consistent with this model, we have identified several predicted PG synthases that are required non-autonomously for sperm guidance (Edmonds et al., 2010). We are using electrospray ionization tandem mass spectrometry, genetic analyses, and in vitro assays to identify roles for these enzymes in PG synthesis. Preliminary data suggest that worms express numerous PG synthases that are essential for synthesizing specific F-series PG types. These enzymes tend to be broadly expressed, raising the possibility that PGs have unknown functions outside of the reproductive system. Another important unanswered question is the mechanism(s) that transduces PG signals in C. elegans sperm, as the genome does not encode obvious homologs of mammalian PG receptors. We have identified mutations in multiple G-protein coupled receptors (GPCRs) that disrupt sperm guidance to the spermatheca. Our data support the hypothesis that these GPCRs function autonomously in sperm. The GPCRs are members of a multi-gene family that is clustered within a chromosomal region enriched in genes important for fertilization (Miller et al., 2004). Mutations in individual GPCRs cause incompletely penetrant defects in sperm guidance, suggesting that their functions partially overlap. We are testing this hypothesis by using the MosDEL transposon-mediated deletion strategy to knock out multiple GPCRs within the cluster. The results may help identify PG receptors in C. elegans.

Pidgeon SE et al. (2017) Bioconjug Chem "Cell Wall Remodeling of Staphylococcus aureus in Live C. elegans."

Pidgeon SE, Pires MM

[Bioconjug Chem, 2017]

Peptidoglycan (PG) scaffolds are critical components of bacterial cell walls. They counter internal turgor pressure to prevent lysis and protect against external insults. It was recently discovered that various types of bacteria release large quantities of PG building blocks (D-amino acids) into their surrounding medium. Cultured bacteria were also found to incorporate D-amino acids (both natural and synthetic) from the medium directly into their PG scaffold. Together, these two processes may potentially function, in concert, to metabolically remodel PG in live host organisms. Yet, demonstration that bacteria can decorate their cell surfaces with exogenous D-amino acids was limited to in vitro culture conditions. We present the first evidence that bacteria remodel their cell wall PG in a live host animal. A tetrazine click partner was conjugated onto the sidechain of a D-amino acid to capture incorporation into the bacterial PG scaffold using a complementary click-reactive fluorophore. Staphylococcus aureus infected Caenorhabditis elegans treated with exogenous D-amino acids readily revealed in vivo PG labeling. These results suggest that extracellular D-amino acids may provide pathogens with a mode of late-stage in vivo cell surface remodeling.

Xu HY et al. (2023) Plant Foods Hum Nutr "Anti-Oxidative and Anti-Aging Effects of Probiotic Fermented Ginseng by Modulating Gut Microbiota and Metabolites in Caenorhabditis elegans."

Zhou WJ, Gong SY, Xu HY, Peng N, Chen ZX, Zhang HB, Li QC, Liu B, Zeng F

[Plant Foods Hum Nutr, 2023]

Antioxidative and antiaging abilities of probiotic fermented ginseng (PG) were evaluated in Caenorhabditis elegans (C. elegans). Lifespan and effect on heat stress and acute oxidative stress in C. elegans were significantly enhanced by PG. Antioxidative enzymes such as T-SOD, GSH-PX, CAT were significantly up-regulated, and MDA, ROS and apoptosis levels were significantly down-regulated. At the same time, PG exerted antioxidant and anti-aging activities by reducing the expression of DAF-2 mRNA and increasing the expression of SKN-1 and SOD-3 mRNA in C. elegans. In addition, the mechanism of antioxidative and antiaging activities of PG was explored through gut microbiota sequencing and untargeted metabolomics. The results of gut microbiota indicated that PG could significantly improve the composition and structure of microbes in the gut of C. elegans, and the relative abundance of beneficial bacteria was up-regulated. Untargeted metabolomic results elucidated that PG modulated antioxidant and antiaging activities through neuroactive ligand-receptor interaction, Citrate cycle (TCA cycle), pyruvate metabolism, ascorbate and aldarate metabolism and D-Arginine and D-ornithine metabolism of C. elegans. These results indicated that PG had excellent antioxidant and anti-aging activities, providing research value for the development of functional foods and improvement of aging-related diseases.

Bennet MD et al. (1983) J Cell Sci "DNA density in mitotic and meiotic metaphase chromosomes of plants and animals."

Ward JP, Smith JB, Bennet MD, Heslop-Harrison JS

[J Cell Sci, 1983]

Studies of chromosome disposition at metaphase using serial thin-sectioning and three-dimensional reconstruction techniques have produced accurate estimates of the total volume of chromosomes per cell in 15 plant and two animal species. Comparing this character with the 4C DNA amount showed no indication of systematic differences in DNA density between either organisms with widely different (>200-fold) C values or different groups or organisms. For example, there was no significant difference between the density of DNA in somatic metaphase chromosomes of man (0.141 pg/um3) and its mean in 14 angiosperm plant species (0.182 pg/um3), or between four dicotyledons (0.180 pg/um3) and 10 monocotyledons (0.182 pg/um3). However, evidence was found showing that DNA density can vary significantly within a species. Thus, although the total chromosome volume per cell was closely correlated (r>0.97) with 4C DNA amount in somatic and meiotic cells, the density of DNA in metaphase chromosomes was significantly lower in meiocytes (0.131 pg/um3) than in somatic metaphase cells (0.179

Kim B et al. (2019) Sci Rep "Differential effects of alkyl gallates on quorum sensing in Pseudomonas aeruginosa."

Choi HY, Kwak JH, Kim B, Kim WG, Park JS

[Sci Rep, 2019]

Virulence factors and biofilms constitute attractive targets for the prevention of infections caused by multidrug-resistant bacteria. Among alkyl gallates, propyl gallate (PG) and octyl gallate (OG) are used as food preservatives. Here we found that alkyl gallates differentially affect virulence, biofilm formation, and quorum sensing (QS) in Pseudomonas aeruginosa. Ethyl gallate (EG), PG, and butyl gallate (BG) inhibited biofilm formation and virulence factors including elastase, pyocyanin, and rhamnolipid, in P. aeruginosa without affecting cell viability by antagonizing the QS receptors LasR and RhlR. PG exhibited the most potent activity. Interestingly, hexyl gallate (HG) inhibited the production of rhamnolipid and pyocyanin but did not affect elastase production or biofilm formation. Notably, OG inhibited the production of rhamnolipid and pyocyanin but stimulated elastase production and biofilm formation. Analysis of QS signaling molecule production and QS gene expression suggested that HG inhibited RhlR, while OG activated LasR but inhibited PqsR. This mechanism was confirmed using QS mutants. Additionally, PG prevented the virulence of P. aeruginosa in Caenorhabditis elegans and a mouse model. This is the first report of the differential effects of alkyl gallates on QS systems and PG has great potential as an inhibitor of the virulence and biofilm formation of P. aeruginosa.

Johansen JL et al. (2019) Ecotoxicol Environ Saf "Wood ash decreases cadmium toxicity to the soil nematode Caenorhabditis elegans."

David MF, Vestergard M, Johansen JL, Ekelund F

[Ecotoxicol Environ Saf, 2019]

Wood ash is a beneficial fertilizer and liming agent in nutrient depleted soils, but it also contains considerable amounts of cadmium (Cd), which can be toxic to organisms in the environment. Therefore, risk assessments regarding utilization of wood ash is required. Here, we studied how wood ash (applied in doses equivalent to 0, 3 and 6t ha^-1) and Cd (applied in doses of 0, 10, 150, 300, 600, 1200 and 2000mgkg^-1) affected growth of the soil nematode Caenorhabditis elegans. The treatments were combined in a full factorial design. Wood ash alone greatly stimulated both soil respiration and growth of C. elegans, whereas Cd alone had a toxic effect. However, unrealistically high Cd levels were needed to severely affect growth of C. elegans and soil respiration, especially soil respiration was very resilient to Cd amendment. Ash addition decreased Cd toxicity to C. elegans, with an EC₅₀ value of 390mgCdkg^-1 in the 3t ash ha^-1 treatment, and an increase of EC₅₀ to 1894mgCdkg^-1 in the 6t ash ha^-1 treatment. This is probably because ash increases the Cd sorption capacity of the soil, and thereby decreases the bio-availability of Cd. The results suggest that there is no acute toxic effect of Cd to nematodes associated with wood ash recycling; in fact, our results suggest that ash actually decrease Cd toxicity.

Shimada A et al. (2010) Z Naturforsch C "Nematicidal activity of beauvericin produced by the fungus Fusarium bulbicola."

Koshino H, Kimura Y, Shimada A, Fujioka S

[Z Naturforsch C, 2010]

A nematicide, beauvericin (1), was isolated from cultures of the fungus Fusarium bulbicola, and its structure was identified by spectroscopic analysis. Compound 1 showed nematicidal activities against the pine wood nematode Bursaphelenchus xylophilus and the free-living nematode Caenorhabditis elegans.

Hu M et al. (2021) Dev Dyn "Mechanisms of TGFB in prostaglandin synthesis and sperm guidance in C. elegans."

Serra R, Prasain JK, Hu M, Tiwary E, Miller M

[Dev Dyn, 2021]

BACKGROUND: The transparent epidermis of C. elegans makes it an attractive model to study sperm motility and migration within an intact reproductive tract. C. elegans synthesize specific F-series prostaglandins (PGFs) that are important for guiding sperm toward the spermatheca. These PGFs are synthesized from polyunsaturated fatty acid (PUFA) precursors, such as arachidonic acid (AA), via a novel pathway, independent of the classical cyclooxygenases (Cox) responsible for most PG synthesis. While the enzyme(s) responsible for PG synthesis has yet to be identified, the DAF-7 TGFB pathway has been implicated in modulating PG levels and sperm guidance. RESULTS: We find that the reduced PGF levels in daf-1 Type I receptor mutants are responsible for the sperm guidance defect. The lower level of PGs in daf-1 mutants is due in part to the inaccessibility of AA. Finally, lipid analysis and assessment of sperm guidance in daf-1;daf-3 double mutants suggest DAF-3 suppresses PG production and sperm accumulation at the spermatheca. Our data suggest that DAF-3 functions in the nervous system, and possibly the germline, to affect sperm guidance. CONCLUSION: The C. elegans TGFB pathway regulates many pathways to modulate PG metabolism and sperm guidance. These pathways likely function in the nervous system and possibly the germline. This article is protected by copyright. All rights reserved.

Manser J et al. (1995) International C. elegans Meeting "CELL MIGRATION GENE PRODUCT MIG-10 IS SIMILAR TO A FAMILY OF SH2 DOMAIN PROTEINS"

Roonprapunt C, Manser J, Margolis B

[International C. elegans Meeting, 1995]

mig-10 is required for the long range antero-posterior migration of embryonic neurons CAN, ALM and HSN and proper development of the excretory canals (Manser and Wood, Dev. Genet. 11: 49-64). Mosaic analysis suggests a cell non-autonomous role for mig-10 in exc canal development.

Panitz D et al. (2015) BMC Pharmacol Toxicol "A C. elegans model of electronic cigarette use: Physiological effects of e-liquids in nematodes."

Swamy H, Panitz D, Nehrke K

[BMC Pharmacol Toxicol, 2015]

BACKGROUND: Electronic cigarettes (e-cigs) have recently become very popular particularly among the younger generation. These nicotine delivery devices are viewed as a preferable alternative to more conventional forms of tobacco use and are thought to reduce the risk of chronic obstructive pulmonary disease, the third leading cause of death worldwide. However, there is very little data available on the consequences of e-cig use, though recently nicotine-independent inflammatory responses have been reported. The genetic model organism Caenorhabditis elegans is a soil nematode whose cell biology is remarkably well conserved with mammals. Here, we used C. elegans to test the physiologic effects of e-liquids used to refill e-cigs. METHODS: Larval worms were exposed from hatching onwards to low concentrations (0.2%) of e-liquids, distilled e-liquid vapor, propylene glycol (PG), or M9 buffer as a negative control. E-liquids tested included grape, menthol, and V2 Red "classic tobacco" flavors. Nicotine (48ppm) was tested as a second level variable. Stereotypical physiological outputs were then measured, including developmental rate, fecundity, locomotion, lifespan, and the induction of canonical stress signaling pathways. RESULTS: A small but significant impairment of developmental rate and brood size was observed for PG and V2 Red treated worms compared to the negative control. Worms treated with e-liquids containing nicotine fared significantly worse than those that did not, but vaporization did not increase toxicity. Finally, both PG and V2 Red e-liquid induced an oxidative stress response in the absence of nicotine. CONCLUSIONS: PG exposure is sufficient to induce an oxidative stress response in nematodes, while nicotine is not. Both PG and nicotine independently influence physiologic measures of health and viability. The e-liquid flavorings did not significantly impact outcomes and there was no evidence for vaporization altering toxicity. These data suggest that the major physiologically significant component of e-liquids besides nicotine is likely the common solvent PG. We conclude that C. elegans are an appropriate model to rapidly assess parameters that may contribute to the basic cell biological effects of e-cigs.