Dataset Information

Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

ABSTRACT: In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy-based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails. We used a recently developed Biomphalaria glabrata oligonucleotide microarray (31K features) to investigate the effect of sublethal exposure to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. Most of the genes highly upregulated following exposure of snails to niclosamide are involved in biotransformation of xenobiotics, including genes encoding cytochrome P450s (CYP), glutathione S-transferases (GST), and drug transporters, notably multi-drug resistance protein (efflux transporter) and solute linked carrier (influx transporter). Niclosamide also induced stress responses. Specifically, six heat shock protein (HSP) genes from three super-families (HSP20, HSP40 and HSP70) were upregulated. Genes encoding ADP-ribosylation factor (ARF), cAMP response element-binding protein (CREB) and coatomer, all of which are involved in vesicle trafficking in the Golgi of mammalian cells, were also upregulated. Lastly, a hemoglobin gene was downregulated, suggesting niclosamide may affect oxygen transport. Our results show that snails mount substantial responses to sublethal concentrations of niclosamide, at least some of which appear to be protective. The topic of how niclosamide's lethality at higher concentrations is determined requires further study. Given that niclosamide has also been used as an anthelmintic drug for decades and has been found to have activity against several types of cancer, our findings may be of relevance in understanding how both parasites and neoplastic cells respond to this compound.

SUBMITTER: Zhang SM

PROVIDER: S-EPMC4599737 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

Zhang Si-Ming SM Buddenborg Sarah K SK Adema Coen M CM Sullivan John T JT Loker Eric S ES

PLoS neglected tropical diseases 20151009 10

In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy-based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology a ...[more]

PMID: 26452273

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Project description:Innate immunity consists of humoral and cellular components that play a vital role in regulation of defense responses to various pathogens in vertebrates and invertebrates. Recent studies have shown that Rel/DIF (dorsal-related immunity factor), Relish, STAT (signal transducer and activator of transcription) and CREB (cAMP response element-binding protein) transcription factor associated pathways are evolutionarily conserved across the animal kingdom. Although the primary role and general structure of the pathways in immunity have been revealed in many invertebrates, particularly arthropods, almost nothing is known about these pathways in the freshwater snail Biomphalaria glabrata, the intermediate host of the human blood fluke Schistosoma mansoni, which is a causative agent of human schistosomiasis. Given the central role of transcription factors (TF) in controlling expression of effector genes, understanding the role of a given TF is essential to obtaining insight into the general function of the corresponding signaling pathway. To better understand the immunity of B. glabrata, we investigated five homologues of TFs that have been shown to be associated with multiple prominent immune signaling pathways based on the considerable data reported from a wide phylogenetic range of animals. In this study we identified and characterized cDNAs of five TFs from B. glabrata, designated BgRelish, BgRel, BgSTAT1, BgSTAT2 and BgCREB, for the first time. Among the five TFs, Relish is first reported in Lophotrochozoa, one of three superphyla in Metazoa. Our identification of class I (BgRelish) and II (BgRel) NF-κB in B. glabrata suggests the two pathways, Toll-like receptor (TLR) and immune deficiency (IMD)-like pathways, are present in the superphylum Lophotrochozoa. Preliminarily expression studies indicate these TF-associated pathways may be involved in the snail's anti-schistosome response. This study not only advances our understanding of the snail's defenses, but also provides new perspectives about the evolution of animal immunity.

Dataset Information

Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

Publications

Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

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