Expression data from Caenorhabditis elegans exposed to ivermectin
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE22660 | GEO | 2011/04/01
SECONDARY ACCESSION(S): PRJNA128009
REPOSITORIES: GEO
Similar Datasets
Project description:We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1?g/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response. Matched cultures of synchronised C. elegans were grown to L4 stage on standard NGM plates with an OP50 bacterial lawn. The nematodes were then transferred to NGM plates containing 100ng/ml ivermectin, 1?g/ml ivermectin, or DMSO excipient only (control) for 4 hours. RNA was extracted from five biological replicates including controls for both the 100ng/ml ivermectin and 1?g/ml ivermectin experiments and hybridised to Affymetrix arrays.
2011-04-01 | E-GEOD-22660 | biostudies-arrayexpress
Project description:The quadruple mutant avr-14(vu47); glc-3(ok321) avr-15(vu227) glc-1(pk54) with avr-15 rescued with a myo-2 promoter for pharynx-specific expression (strain LRB269) was used. This allowed worms to perceive food but not eat it when the drug ivermectin is added.
2018-09-20 | GSE114955 | GEO
Project description:Ascarid parasites infect a variety of hosts, and control measures rely heavily on anthelmintics raising concerns for anthelmintic resistance. Parascaris spp., the equine ascarid, is the only ascarid with documented substantial drug resistance. Elucidating drug responses of susceptible parasites may lead to further understanding of anthelmintic resistance mechanisms, identifying alternative drug targets, and parameters for slowing the development of resistance among other ascarid species. The purpose of this study was to examine the response of anthelmintic naïve Parascaris spp. to in vitro drug exposure using transcriptomic analyses and quantitative PCR. Adult Parascaris spp. worms were obtained at necropsy from foals born into a herd kept without anthelmintic treatment. Adult worms were maintained in Roswell-Park Memorial medium 1640. The drugs employed were oxibendazole (OBZ) and ivermectin (IVM), and 10-fold serial dilutions were prepared. Optimum drug concentration and exposure length were determined using a worm viability assessment method. Subsequently, RNA-seq analysis identified genes with significantly different expression between drug treated and control groups. Finally, a selection of the significant genes was further investigated using qPCR in a repeat drug exposure trial. Following initial viability assessments, OBZ (10 μg/mL) for 24 hours and IVM (1 μg/mL) for three hours were the conditions employed. RNA-seq analysis revealed a total of 88 transcripts with significantly (α=0.01) different expression between all drug treated and control worms. The top five genes selected for further analysis were snap25, cytochrome p450, kelch10, sup9, and ferm. Gene functionalities are related to muscle contraction, detoxification and exocytotic events, and regulatory processes. qPCR did not identify any significant differences between groups, but this may be due to the lack of method sensitivity. The results of RNA-seq analysis and gene function warrant further investigation and their role in ascarid xenobiotic responses.
2019-04-10 | GSE129514 | GEO
Project description:Rhipicephalus microplus is among the critical tick parasite of cattle farming globally. However, the massive use of ivermectin last decades induced the generation of the tick-resistant population. Unfortunately, despite extensive research the mode of action of ivermectin remains unclear. Due to the limited molecular information related to the resistance of R. microplus to ivermectin, we carried out a midgut comparative proteomics study between susceptible and resistant tick. Our tissues specificity approach also included tandem mass tags (TMT) couple to synchronous precursor selection (SPS)-MS3. Our proteomics scrutiny exhibits key biological process associated with blood digestion and anticoagulation in midgut. In addition, we could observe the significant shutdown of the translation mechanism in susceptible thinks. At the same time, resistant thick exhibited the over-accumulation of cytochrome P450, glutathione-S-transferase, and ABC transporters. A similar trend was observed in proteins like glutathione peroxides glutaredoxin, sulfiredoxin, and disulfide-isomerase, which suggest a possible activation of the oxidative metabolism as a potential strategy to cope with ivermectin treatment.
2024-01-29 | PXD031231 | Pride
Project description:Ticks are among the most economically important arthropod parasites due to the heavy infestations they provoke, affecting human and animal health and food production. Ticks are also important vectors of pathogens, mediating the dispersion of livestock and zoonotic diseases. Some examples of livestock diseases vectored by ticks include bovine babesiosis, anaplasmosis, theileriosis, and/or heartwater disease, all of which are enlisted by the World Organization for Animals as possible threats to animals and public health. The family Ixodidae (hard ticks) is of veterinary relevance, and many ixodid tick species within the genera Ixodes, Dermacentor, Amblyomma, Haemophysalis, Hyalomma, and Rhipicephalus, among others, impact farming production worldwide. However, there is no doubt that most pernicious tick species is Rhipicephalus microplus, commonly known as the southern cattle fever tick. This specie is not only the major economically important tick parasite for livestock production, but it is also the vector of Babesia bovis and B. bigemina, the causal agents of babesiosis, a severe disease that affects cattle from tropical and subtropical regions. Currently, global economic losses of the cattle industry attributable to R. microplus are estimated at around $18.7 US billion dollars per year. The economic impact is the leading reason to develop different strategies to constrains R. microplus and its vector-borne pathogens, including chemical, mechanical or environmental treatments, biological control, and/or genetic methods. Chemical, among other methods, are the most frequently applied, but the intense use worldwide, has led to the selection of acaricidal-resistant ticks populations. The molecular adaptations of ticks to overcome the effects of acaricides (e.g., deltamethrin, cypermethrin, amitraz, ivermectin) includes metabolic detoxification mechanisms and/or the selection of mutated molecular targets. Recently, a couple of systematic reviews pointed out a significant increment in the number of studies intended to understand the acaricidal resistance in ticks. These reports highlighted the acaricide resistance observed in R. microplus and the wide geographical dispersion of this problem. Whereas many acaricide-resistant R. microplus populations have been reported in Brazil, India, and Mexico, the lack of strict regulatory policies on tick control, leaving the application of acaricides at discretion of farmers. Therefore, the correct implementation of existing strategies together with novel sustainable control methods may be crucial to safeguard livestock production in the context of growing population and global warming. However, until the implementation of such sanitary measures becomes the rule, the main control strategy will still rely on the use of chemical acaricides, such as ivermectin (IVM). Ivermectin is an antiparasitic macrocyclic lactone used to control the populations of R. microplus and other ticks in livestock farming. As occurs in other countries, in Mexico ivermectin is the primary synthetic antiparasitic drug, and its abuse during the last three decades represents an important selection pressure that boosted the development of ivermectin-resistant populations of R. microplus. Therefore, the understanding of the molecular basis of the R. microplus resistance to ivermectin, especially in those cases occurring in tropical and subtropical areas of developing countries, can help to underpin the development of novel strategies to tackle this problem. In this context, omics tools can provide helpful information for the discovery of the molecular mechanisms behind the ivermectin resistance in R. microplus and other related tick species. Previous studies identified the main proteomic components of ovaries of R. microplus, including proteins involved in protein synthesis, post-translational modification, nuclear regulation, cytoskeleton, proteasome, transcriptional regulation, energetic metabolism, detoxification metabolism, or energy storage. Recently, the vitellogenin receptor (VgR) was suggested as a target for tick control because of its essential role in egg formation and maturation. However, molecular information on tick ovaries currently available limits explores the feasibility of VgR or other reproduction-related molecules as promissory targets for tick control.
2024-01-29 | PXD034493 | Pride
Project description:Here, we show that ivermectin suppress prostate cancer progression by inhibiting AR signaling pathway and attenuate cellular DNA damage repair capacity. We applied an integrated omics profiling including RNA-seq and Thermal proteome, that found pioneer factor Forkhead Box Protein A1 (FOXA1) and Non-homologous End Joining (NHEJ) repair executer Ku70/Ku80 was the direct target of Ivermectin in prostate cancer. Ivermectin binds to these two proteins and block their biological function, which results in blockade of AR signaling transcription and deficiency of DNA double-strand breaks (DSBs) repair system, and thereby leads to G0/G1 arrest and trigger synthetic lethality Our findings demonstrate both the effect and target of Ivermectin in prostate cancer comprehensively and systemically, indicating that use of Ivermectin may constitute a new therapeutic approach for prostate cancer.
2022-04-01 | GSE169356 | GEO
Project description:Anthelmintic resistance is a major problem in the global fight against parasitic nematodes., Most previous studies have focused on the analysis of potential candidate genes that may have a role in resistance. Here we take a novel approach in the important parasite, Haemonchus contortus, by investigating changes in microRNA expression between resistant and susceptible parasites. The resistant worms included two geographically distinct strains and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed increased abundance of a single miRNA, hco-miR-9551, compared to the susceptible strain. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is found only in clade V parasitic nematodes. Approximately 5-10% of the genomes of the resistant parental strains are introgressed into the respective backcrosses, suggesting that hco-miR-9551, or genes regulated by the miRNA, may be genetically linked to a locus that determines resistance. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset. These findings advance our conceptual understanding of the molecular mechanisms of anthelmintic resistance in H. contortus and indicate that altered miRNA expression may be linked with drug resistance. All samples were carried out using three biological replicates
2016-03-25 | E-GEOD-79542 | biostudies-arrayexpress
Project description:Anthelmintic resistance is a major problem in the global fight against parasitic nematodes., Most previous studies have focused on the analysis of potential candidate genes that may have a role in resistance. Here we take a novel approach in the important parasite, Haemonchus contortus, by investigating changes in microRNA expression between resistant and susceptible parasites. The resistant worms included two geographically distinct strains and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed increased abundance of a single miRNA, hco-miR-9551, compared to the susceptible strain. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is found only in clade V parasitic nematodes. Approximately 5-10% of the genomes of the resistant parental strains are introgressed into the respective backcrosses, suggesting that hco-miR-9551, or genes regulated by the miRNA, may be genetically linked to a locus that determines resistance. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset. These findings advance our conceptual understanding of the molecular mechanisms of anthelmintic resistance in H. contortus and indicate that altered miRNA expression may be linked with drug resistance.
2016-03-25 | GSE79542 | GEO
Project description:OCI AML2 cells were treated with the anti-parasitic ivermectin (single dose, two time points) in order to assess gene expression changes.
2010-01-06 | E-MEXP-2528 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include “maternal sterile”, “embryonic lethal”, “larval arrest”, “larval lethal”, “reduced brood size” and “egg shape variable”. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
2016-07-27 | GSE75340 | GEO