Ji K et al. (2015) Food Funct "Inhibition effects of tanshinone on the aggregation of -synuclein."

Liu Y, Ji K, Zhao Y, Yang X, Gong H, Huang K, Wang Z, Yu T

[Food Funct, 2015]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated -synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on -synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of -synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of -synuclein from unstructured coils to -sheets, and alleviated the membrane disruption caused by aggregated -synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human -synuclein, possibly by attenuating the aggregation of -synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.

Zhang X et al. (2022) Free Radic Biol Med "Tanshinone IIA loaded chitosan nanoparticles decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease"

Zhang X, Chang Y, Du L, Wang J, Zhang L, Wang S, Kang X, Liu Y, Zhao Y, Huang Y

[Free Radic Biol Med, 2022]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA (CS@Tan IIA) and explore the protective effects of CS@Tan IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, CS@Tan IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of CS@Tan IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of CS@Tan IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.

Dahl JL et al. (2011) J Bacteriol "Role of phase variation in the resistance of Myxococcus xanthus fruiting bodies to Caenorhabditis elegans predation."

Ulrich CH, Kroft TL, Dahl JL

[J Bacteriol, 2011]

The phenomenon of phase variation between yellow and tan forms of Myxococcus xanthus has been recognized for several decades, but it is not known what role this variation may play in the ecology of myxobacteria. We confirm an earlier report that tan variants are disproportionately more numerous in the resulting spore population of a M. xanthus fruiting body than the tan vegetative cells that contributed to fruiting body formation. However, we found that tan cells may not require yellow cells for fruiting body formation or starvation-induced sporulation of tan cells. Here we report three differences between the yellow and tan variants that may play important roles in the soil ecology of M. xanthus. Specifically, the yellow variant is more capable of forming biofilms, is more sensitive to lysozyme, and is more resistant to ingestion by bacteriophagous nematodes. We also show that the myxobacterial fruiting body is more resistant to predation by worms than are dispersed M. xanthus cells.

Muir RE et al. (2008) Appl Environ Microbiol "Virulence of Leucobacter chromiireducens subsp. solipictus to Caenorhabditis elegans: characterization of a novel host-pathogen interaction."

Tan MW, Muir RE

[Appl Environ Microbiol, 2008]

We describe the pathogenic interaction between a newly described Gram-positive bacterium Leucobacter chromiireducens subsp. solipictus strain TAN 31504 and the nematode Caenorhabditis elegans. TAN 31504 pathogenesis on C. elegans is exerted primarily through infection of the adult nematode uterus. TAN 31504 enters the uterus through the external vulval opening and the ensuing uterine infection is strongly correlated with a significant reduction in host life span. Young worms can fed and develop on TAN 31504, but not preferably over the standard food source. C. elegans reared on TAN 31504 as the sole food source develop into thin adults with little intestinal fat stores, produce few progeny, and subsequently can not persist on the pathogenic food source. Within 12 h of exposure, adult worms challenged with TAN 31504 alter the expression of a number of C. elegans innate immunity-related genes, including nlp-29, which encodes a neuropeptide-like protein. C. elegans exposed briefly to TAN 31504 develop lethal uterine infections analogous to worms exposed continuously to pathogen, suggesting that mere contact with the pathogen is sufficient for the host to become infected. TAN 31504 produces a robust biofilm and this behavior is speculated to play a role in the virulence exerted on the nematode host. The interaction between TAN 31504 and C. elegans provides a convenient opportunity to study bacterial virulence on nematode tissues other than the intestine and may allow for the discovery of host innate immunity elicited specifically in response to vulval-uterine infection.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).

Terskikh A et al. (2000) Science ""Fluorescent timer": protein that changes color with time."

Matz M, Ermakova G, Siebert P, Kim SK, Lukyanov S, Kajava AV, Weissman I, Zaraisky A, Terskikh A, Tan PBO, Fradkov A, Zhao X

[Science, 2000]

We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and down-regulation of target promoters on the whole-organism scale.AD - School of Medicine, Stanford University, Stanford, CA 94305, USA. Alexey.Terskikh@Stanford.eduFAU - Terskikh, AAU - Terskikh AFAU - Fradkov, AAU - Fradkov AFAU - Ermakova, GAU - Ermakova GFAU - Zaraisky, AAU - Zaraisky AFAU - Tan, PAU - Tan PFAU - Kajava, A VAU - Kajava AVFAU - Zhao, XAU - Zhao XFAU - Lukyanov, SAU - Lukyanov SFAU - Matz, MAU - Matz MFAU - Kim, SAU - Kim SFAU - Weissman, IAU - Weissman IFAU - Siebert, PAU - Siebert PLA - engID - 1 RO3 TW01362-01/TW/FICPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Heat-Shock Proteins)RN - 0 (Luminescent Proteins)RN - 0 (Nerve Tissue Proteins)RN - 0 (Otx2 protein)RN - 0 (Trans-Activators)RN - 0 (red fluorescent protein)SB - IM

Asif, Muhammad Zaka et al. (2021) MicroPubl Biol

Van der Gaag, Victoria L., Edison, Arthur S., Muzio, Cole J., Asif, Muhammad Zaka, Nocilla, Kelsey A., Guo, Jane

[MicroPubl Biol, 2021]

1-Hydroxyphenazine (1-HP) is a small molecule produced by Pseudomonas aeruginosa, a bacterium that is used for pathogenesis models in C. elegans (Cezairliyan et al., 2013; Mahajan-Miklos, Tan, Rahme, & Ausubel, 1999). 1-HP is an especially interesting toxin to study as it has been shown to interact with human cells causing ciliary-slowing associated with dyskinesia and ciliostasis (Wilson et al., 1987). Prior research in our lab has shown that this molecule is toxic to C. elegans, with an LD50 between 150 and 200 M, but C. elegans can glycosylate 1-HP, which detoxifies the molecule (Stupp et al., 2013).

Catherine A Mastroieni et al. (2004) West Coast Worm Meeting "ANALYSIS OF MAP KINASE PHOSPHORYLATION SITES IN THE C. ELEGANS TRANSCRIPTION FACTOR LIN-31"

Corey A Morris, Catherine A Mastroieni, Leilani M Miller

[West Coast Worm Meeting, 2004]

Complex signaling pathways are required for the proper specification of cell fates. In the C. elegans hermaphrodite, six cells of initially equivalent developmental potential respond differentially to a Ras/MAP kinase signaling pathway, correctly choosing their respective fates to form the adult vulva. Activation of the Ras/MAP kinase pathway culminates in the phosphorylation of one or more transcription factors by MAP kinase, resulting in the induction of fate-specific genes. One of the transcription factors phosphorylated by MAP kinase is LIN-31, a winged-helix transcription factor (Miller et al., Genes Dev. 7:933, 1993) that contains four consensus MAP kinase phosphorylation sites. Co-immunoprecipitation experiments by Tan et al. (Cell 93:569, 1998) showed that LIN-31 forms a heterodimer with the LIN-1 ETS transcription factor and that this heterodimer is disrupted upon phosphorylation of LIN-31 by MAP kinase. These results support the following model in which LIN-31 has two functions: 1) in its unphosphorylated, dimerized form LIN-31 promotes non-vulval cell fates, and 2) in its phosphorylated, undimerized form LIN-31 promotes vulval cell fates. Consistent with the model that phosphorylation of the MAP kinase consensus sites is necessary for LIN-31 function in promoting vulval cell fates, previous studies (Tan et al., 1998) have shown that deletion of all four phosphorylatable sites in LIN-31 results in defective vulval formation. Since the core sequence for MAP kinase consensus sites (S/T-P) consists of only two amino acids, many "consensus" sites identified by sequence alone may not actually be phosphorylated by MAP kinase. Although the first MAP kinase phosphorylation site in the LIN-31 protein is a "full" site (P-X-S/T-P) and Tan et al. (1998) showed that removal of this site resulted in a 50% decrease in overall phosphorylation of the LIN-31 protein, the other three sites contain only the "core" sequence. We are using site-directed mutagenesis, protein expression and purification, and phosphorylation experiments to investigate the phosphorylation pattern of the putative MAP kinase phosphorylation sites in the LIN-31 protein.

Ewbank JJ et al. (2000) European Worm Meeting "Using C. elegans to identify Serratia marcescens virulence factors"

Ewbank JJ, Kurz CL, Finlay BB, Celli J

[European Worm Meeting, 2000]

Tan and Ausubel, working with the enterobacterium Pseudomonasaeruginosa, have established C. elegans as a model for the study of pathogenesis and host defences. Clearly, the use of the worm as a model for studying pathogenicity will be limited to those pathogens that are able to infect the worm. Luckily, in this respect, its susceptibility to P. aeruginosaappears not to be an isolated case. A second opportunistic human pathogen, Serratia marcescens, is also capable of infecting C. elegans. Like P. aeruginosa, S. marcescens is able to infect a broad range of plant and animal hosts and has been used as a model pathogen in studies of Drosophila innate immunity. Using a strain of S. marcescensthat expresses GFP, we have been able to follow the infection process. The bacteria are able to survive within the usually hostile environment of the nematode intestine, proliferate and kill the host. Under standard assay conditions, the progression of the infection is highly reproducible. We have used a transposon mutagenesis system to create a library of insertion mutants of S. marcescens. We are currently screening these mutant bacterial clones individually for those showing reduced virulence.Of the first 2000 mutants screened, 18 showing markedly reduced virulence have been retained for further study. The molecular characterization of these mutants may reveal novel virulence factors that represent potential drug targets. Tan MW, Ausubel FM. (2000) Caenorhabditis elegans: a model genetic host to study Pseudomonas aeruginosa pathogenesis. Curr Opin Microbiol. S: 29-34.

Rich T et al. (2000) Immunogenetics "Pellino-related sequences from Caenorhabditis elegans and Homo sapiens."

Rich T, Allen RL, Stewart A, Trowsdale J, Lucas AM

[Immunogenetics, 2000]

Toll receptor systems play an important role in our innate immune response to microbial infection (Rock et al. 1998). Studies of related pathways in arthropods (Hoffmann et all. 1999; Imler and Hofmann 2000) have led to key advances in our understanding of these processes. Until recently, however, the possibility that Toll signals may activate both immune and/or developmental pathways in Caenorhabditis elegans has been largely ignored. Early failures to identify Toll receptors or NFB-like transcription factors in the C. elegans genome (Ruvkun and Hobert 1998) let to the assumption that its Toll pathway was inoperable. Therefore, given the paucity of knowledge on innate immune responses for these animals, there was no impetus to develop C. elegans pathogenicity models. Recent database searches, however, have identified components of the elusive C. elegans Toll receptor pathway (Rich et al. 2000; Tan et al. 1999). The existence of a rudimentary immune response is further supported by evidence that antimicrobial peptides are encoded within the C. elegans genome (Tan and Ausubel 2000). In fact, C. elegans is susceptible to infection from several different pathogens, making this genetically tractable invertebrate an attractive model to study host-pathogen interactions. These developments are particularly important for the study of pathogens such as Pseudomonas aeruginosa whose natural hosts include humans. A suitable C. elegans model could, for example, provided a rapid system to screen candidate antibacterial drugs. Consequently, it has now become important to identify and isolate cDNAs for each component of the C. elegans Toll pathway.