Drug repurposing of bromodomain inhibitors as potential novel therapeutic leads for lymphatic filariasis guided by multi-species transcriptomics
Ontology highlight
ABSTRACT:
ORGANISM(S): Aedes aegypti Brugia malayi Wolbachia endosymbiont of Brugia malayi
PROVIDER: GSE139965 | GEO | 2019/11/20
REPOSITORIES: GEO
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2012-01-16 | GSE34976 | GEO
Project description:Doxycycline treatment affects gene expression in Wolbachia and Brugia malayi adult female worms in vivo Two biological replicates of female RNA used for hybridization, in duplicate, to examine the gene expression changes in Wolbachia and Brugia
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Project description:The filarial nematodes Brugia malayi, Wuchereria bancrofti and Onchocerca volvulus cause elephantiasis, dermatitis and blindness, resulting in severe morbidity in developing countries. 1.3 billion people are at risk of infection. Targeting the essential Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy, resulting in a block in embryogenesis and worm development, and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at-risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the Wolbachia-filaria symbiosis is required. We performed cross-species hybridization by using the Brugia malayi microarray to identify differentially expressed genes in the rodent filaria Litomosoides sigmodontis after depletion of Wolbachia which therefore might have a role in symbiosis.
2010-04-07 | GSE20976 | GEO
Project description:Parasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners. Here we conduct a joint dual RNA-seq time course analysis of filarial parasite and host mosquito to better understand the parasite processes underlying development in, and interaction with, the host tissue from the establishment of infection to the emergence of infective-stage larva. Using the Brugia malayi-Aedes aegypti system, we report the parasite gene transcription dynamics, which exhibit a highly ordered developmental program consisting of a series of cyclical and state-transitioning temporal patterns. And, we contextualize these parasite data in relation to the concurrent dynamics of the host transcriptome. Comparative analyses using uninfected tissues and different host strains reveal the influence of parasite development on the host gene transcription as well as the influence of host environment on the parasite gene transcription. Furthermore, we critically evaluate the life-cycle transcriptome of B. malayi by comparing developmental stages in the mosquito relative to those in the mammalian host, providing insight into gene expression changes underpinning the mosquito-borne parasitic lifestyle of this heteroxenous parasite. Time-course mRNA profiles of filarial parasite Brugia malayi and host mosqutio Aedes aegypti were generated by deep sequencing using Illumina GAIIx.
2014-04-15 | E-GEOD-53664 | biostudies-arrayexpress
Project description:Wolbachia endosymbiont of Brugia malayi strain:wBm Raw sequence reads
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Project description:The filarial nematodes Brugia malayi, Wuchereria bancrofti and Onchocerca volvulus cause elephantiasis, dermatitis and blindness, resulting in severe morbidity in developing countries. 1.3 billion people are at risk of infection. Targeting the essential Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy, resulting in a block in embryogenesis and worm development, and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at-risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the Wolbachia-filaria symbiosis is required. We performed cross-species hybridization by using the Brugia malayi microarray to identify differentially expressed genes in the rodent filaria Litomosoides sigmodontis after depletion of Wolbachia which therefore might have a role in symbiosis. Female adult Litomosoides sigmodontis from patent infections were treated with tetracycline to deplete endosymbiotic Wolbachia bacteria. RNA from tetracycline-treated Litomosoides sigmodontis was compared to untreated age-matched control worms. This experiment was performed for three different timepoints: day 6, 15 and 36 of tetracycline treatment. One biological replicate was performed each with two technical replicates (dye-flip replicates).
2010-04-07 | E-GEOD-20976 | biostudies-arrayexpress
Project description:To observe the global changes in the lymphatic endothelial cells upon exposure to filarial antigens or parasites, LECs were stimulated for 24, 48, and 72hrs and the expression profiles were carried out. Human filarial parasites Brugia malayi and Wuchereria bancrofti habitat the lymphatics and cause lymphatic dilatation and lymphedema. In order to evaluate the effect of various stage specific effects on the lymphatic endothelial cells (LEC) and understand how they modulate the lymphatic dysfunction, LECs were stimulated in antigens derived from the Brugia malayi. These are preliminary time course data towards understanding how the filarial antigens induce lymphangiogenesis.
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Project description:Lymphatic filarial nematodes maintain a mutualistic association with the intracellular bacterium Wolbachia. Wolbachia populations expand following infection of the mammalian host, to support larval growth and development. Utilizing transcriptomic data from Brugia malayi over the first two weeks post-infection, we present an analysis of the biochemical pathways that are involved in Wolbachia population growth and regulation in support of larval development. In Wolbachia, we observe coordinated regulation of carbon metabolism with an alternating pattern of glycolysis and TCA cycle pathways reminiscent of the ‘Warburg effect’. Wolbachia's purine, pyrimidine and haem biosynthesis and Type IV secretion pathways are also upregulated and correlate with the upregulation of the nematode’s DNA replication pathway. In the nematode we observe up-regulation of the autophagy pathway, a key regulator of Wolbachia populations. These findings support a key role for nucleotide and haem provisioning from Wolbachia in support of the larval growth and development of its nematode host.
2021-06-30 | GSE132848 | GEO
Project description:Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. A total of 178 novel microRNA were identified from short read transcriptional data, which when combined with known Brugia microRNAs yielded a total of 284 microRNA. Of these, 123 microRNA sequences (43%) are differentially expressed over the mammalian life stages of B. malayi that we examined. Putative targets of these microRNA were identified from inversely expressed target clusters that contain valid seed sequences for the corresponding microRNAs. The largest identified cluster is downregulated in adult females and enriched in zinc finger domains, helicase domains, and DNA binding domains suggesting this microRNA cluster may have regulatory control over a large proportion of adult female specific mRNA genes. MicroRNA-like molecules are identified as produced by the Wolbachia endosymbiont, providing evidence for direct nucleic acid-based interdomain communication between filarial nematodes and their bacterial obligate endosymbiont.
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