Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide
نویسندگان
چکیده
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.
منابع مشابه
The molluscicidal activity of niclosamide (Bayluscide WP70(R)) on Melanoides tuberculata (Thiaridae), a snail associated with habitats of Biomphalaria glabrata (Planorbidae).
The aim of this study was to determine the toxicity of niclosamide (Bayluscide (R)) on Melanoides tuberculata and Biomphalaria glabrata under laboratory conditions. The latter species is the intermediate host of Schistosoma mansoni (Sambon 1917). M. tuberculata was successfully used as competitor of B. glabrata in biological control programs in French West Indies. Both molluscicide and biologic...
متن کاملEarly Differential Gene Expression in Haemocytes from Resistant and Susceptible Biomphalaria glabrata Strains in Response to Schistosoma mansoni
The outcome of infection in the host snail Biomphalaria glabrata with the digenean parasite Schistosoma mansoni is determined by the initial molecular interplay occurring between them. The mechanisms by which schistosomes evade snail immune recognition to ensure survival are not fully understood, but one possibility is that the snail internal defence system is manipulated by the schistosome ena...
متن کاملDifferences in the Gene Expression Profiles of Haemocytes from Schistosome-Susceptible and -Resistant Biomphalaria glabrata Exposed to Schistosoma mansoni Excretory-Secretory Products
During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs) that likely influence the ou...
متن کاملThe Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni
BACKGROUND The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail's response to infection. METH...
متن کاملHistorical Perspective: Snail Control to Prevent Schistosomiasis
Effective interruption of the Schistosoma life cycle is essential to blocking the parasite’s transmission, and thus truly preventing human schistosomiasis over the long term. Our current mass treatment campaigns were expected to limit transmission by reducing environmental contamination with parasite eggs. However, the process of transmission has proven to be very focal and highly efficient, su...
متن کامل