scholarly journals Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors

2019 ◽  
Vol 13 (12) ◽  
pp. e0006927
Author(s):  
Sarah K. Buddenborg ◽  
Bishoy Kamel ◽  
Lijing Bu ◽  
Si-Ming Zhang ◽  
Gerald M. Mkoji ◽  
...  
2018 ◽  
Author(s):  
Sarah K. Buddenborg ◽  
Bishoy Kamel ◽  
Si-Ming Zhang ◽  
Gerald M. Mkoji ◽  
Eric S. Loker

abstractBackgroundSchistosomiasis is one of the world’s most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including forBiomphalaria pfeifferi, the most important vector forSchistosoma mansoniin Africa. We used Illumina technology to explore how field-derivedB. pfeifferi, either uninfected or harboring cercariae–producingS. mansonisporocysts, respond to a sublethal exposure of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is exposed to niclosamide.Principal FindingsCercariae-producing sporocysts within snails exposed to niclosamide express ~68% of the genes in theS. mansonigenome, as compared to 66% expressed by intramolluscan stages ofS. mansoniin snails not exposed to niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. ForB. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.Conclusions/SignificanceThis study helps define the transcriptomic responses of an important and under-studied schistosome vector toS. mansonisporocysts, to niclosamide, and to both in combination. It suggests the response ofS. mansonisporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails.Author’S SummarySchistosomaisis control programs often employ the use of chemical molluscicides, such as niclosamide, to control the obligatory intermediate snail hosts. Despite its widespread use, we know little about how niclosamide affects snails likeBiomphalaria pfeifferi, the most important vectorSchistosoma mansoniin Africa. By sequencing the transcriptomes of uninfected andS. mansoni-infectedB. pfeifferiexposed to niclosamide, we analyze the snail’s response to both biotic and abiotic stressors. We can also examine the response ofS. mansonito niclosamide exposure during intramolluscan development.Biomphalaria pfeifferisnails exposed only to niclosamide showed unique up-regulation of stress and defense-related transcripts not seen in snails infected with a biotic, likeS. mansoniinfection, alone.Schistosoma mansoni-infectedB. pfeifferiexposed to niclosamide were clearly unable to regulate normal metabolic and detoxification processes. Cercariae-producing sporocysts within snails exposed to niclosamide are largely unaffected and continue to produce transcripts required for cercariae production.


2018 ◽  
Author(s):  
Sarah K. Buddenborg ◽  
Bishoy Kamel ◽  
Ben Hanelt ◽  
Lijing Bu ◽  
Si-Ming Zhang ◽  
...  

ABSTRACTBackgroundThe full scope of the genes expressed by schistosomes during intramolluscan development has yet to be characterized. Understanding the gene products deployed by larval schistosomes in their snail hosts will provide insights into their establishment, maintenance, asexual reproduction, ability to castrate their hosts, and their prolific production of human-infective cercariae. Using the Illumina platform, the intramolluscan transcriptome ofSchistosoma mansoniwas investigated in field-derived specimens of the prominent vector speciesBiomphalaria pfeifferiat 1 and 3 days post infection (d) and from snails shedding cercariae. TheseS. mansonisamples were derived from the same snails used in our complementaryB. pfeifferitranscriptomic study. We supplemented this view with microarray analyses ofS. mansonifromB. glabrataat 2d, 4d, 8d, 16d, and 32d.Principal FindingsTranscripts representing at least 7,740 (66%) of knownS. mansonigenes were expressed during intramolluscan development, with the greatest number expressed in snails shedding cercariae. Many transcripts were constitutively expressed throughout development featuring membrane transporters, and metabolic enzymes involved in protein and nucleic acid synthesis and cell division. Several proteases and protease inhibitors were expressed at all stages, including some proteases usually associated with cercariae. Transcripts associated with G-protein coupled receptors, germ cell perpetuation, and stress responses and defense were well represented. We noted transcripts homologous to planarian anti-bacterial factors, several neural development or neuropeptide transcripts including neuropeptide Y, and receptors that may be associated with schistosome germinal cell maintenance and that could also impact host reproduction. In at least one snail the presence of larvae of another digenean species (an amphistome) was associated with repressedS. mansonitranscriptional activity.Conclusions/SignificanceThisin vivostudy, particularly featuring field-derived snails and schistosomes, provides a distinct view from previous studies of development of cultured intramolluscan stages from lab-maintained organisms. We found many highly represented transcripts with suspected or unknown functions, with connection to intramolluscan development yet to be elucidated.AUTHOR SUMMARYSchistosoma mansoniis one of the most important schistosome species causing the neglected tropical disease human intestinal schistosomiasis. By focusing onS. mansoni in vivowith its broadly distributed sub-Saharan African snail intermediate host,Biomphalaria pfeifferi, we uncover new insights and basic knowledge of this host-parasite relationship that are critical for understanding schistosomiasis transmission. We show thatin vivostudies, particularly using field-derived specimens, provides a distinct view from the uniformed transcriptional responses traditionally seen fromin vitrostudies onS. mansoniandBiomphalariasnails. With the growing consensus that we need to supplement chemotherapy with other control methods, understanding howS. mansoniinteracts with its obligatory snail host becomes integral for future planning of control programs. The data provided within provides specific analysis on how the schistosomes successfully protect themselves from host defenses and the necessary transcriptional responses required for its amplifying asexual proliferation that result in human-infective cercariae.


2012 ◽  
Vol 132 (4) ◽  
pp. 501-507 ◽  
Author(s):  
M. Ibikounlé ◽  
G. Mouahid ◽  
R. Mintsa Nguéma ◽  
N.G. Sakiti ◽  
D. Kindé-Gasard ◽  
...  

Parasitology ◽  
1994 ◽  
Vol 109 (4) ◽  
pp. 443-453 ◽  
Author(s):  
R. F. Sturrock ◽  
R. K. Klumpp ◽  
J. H. Ouma ◽  
A. E. Butterworth ◽  
A. J. C. Fulford ◽  
...  

SUMMARYTransmission of Schistosoma mansoni was monitored by routine snail sampling for Biomphalaria pfeifferi and by supplementary cercariometric measurements in 4 neighbouring study areas in Machakos District, Kenya. After 1 year, extensive, population-based chemotherapy with a single dose of praziquantel was given in 3 areas, but only minimal treatment in the fourth. In the year preceding treatment, seasonal transmission of S. mansoni and other non-human trematodes occurred in all 4 areas, despite some ecological differences and the effects of earlier treatment campaigns in 1 of the study areas. After treatment of all infected subjects in one area in which there had been earlier chemotherapy campaigns, S. mansoni transmission remained very low. It was reduced for at least 2 years after chemotherapy targeted at either all heavily infected subjects or all infected school children, but it was unaffected in an area where treatment was restricted to those few very heavily infected cases at risk of developing, disease. Nowhere was transmission entirely eliminated by chemotherapy and that of non-human trematodes continued unabated. The snail data correspond well with the human, parasitological data. Targeting school children was as effective as more extensive campaigns, but chemotherapy alone never stopped S. mansoni transmission: reinfection was inevitable, at rates determined by ecological factors affecting snail populations.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lijun Lu ◽  
Lijing Bu ◽  
Si-Ming Zhang ◽  
Sarah K. Buddenborg ◽  
Eric S. Loker

BackgroundWe seek to provide a comprehensive overview of transcriptomics responses of immune-related features of the gastropod Biomphalaria glabrata (Bg) following exposure to Schistosoma mansoni (Sm), a trematode causing human schistosomiasis. Responses of schistosome-susceptible (M line, or SUS) and -resistant (BS-90, or RES) Bg strains were characterized following exposure to Sm for 0.5, 2, 8 or 40 days post-exposure (dpe).MethodsRNA-Seq and differential expression analysis were undertaken on 56 snails from 14 groups. We considered 7 response categories: 1) constitutive resistance factors; 2) constitutive susceptibility factors; 3) generalized stress responses; 4) induced resistance factors; 5) resistance factors suppressed in SUS snails; 6) suppressed/manipulated factors in SUS snails; and 7) tolerance responses in SUS snails. We also undertook a gene co-expression network analysis. Results from prior studies identifying schistosome resistance/susceptibility factors were examined relative to our findings.ResultsA total of 792 million paired-end reads representing 91.2% of the estimated 31,985 genes in the Bg genome were detected and results for the 7 categories compiled and highlighted. For both RES and SUS snails, a single most supported network of genes with highly correlated expression was found.Conclusions1) Several constitutive differences in gene expression between SUS and RES snails were noted, the majority over-represented in RES; 2) There was little indication of a generalized stress response shared by SUS and RES snails at 0.5 or 2 dpe; 3) RES snails mounted a strong, multi-faceted response by 0.5 dpe that carried over to 2 dpe; 4) The most notable SUS responses were at 40 dpe, in snails shedding cercariae, when numerous features were either strongly down-regulated indicative of physiological distress or parasite manipulation, or up-regulated, suggestive of tolerance or survival-promoting effects; 5) Of 55 genes previously identified in genome wide mapping studies, 29 (52.7%) were responsive to Sm, as were many familiar resistance-associated genes (41.0%) identified by other means; 6) Both network analysis and remarkably specific patterns of expression of lectins and G protein-coupled receptors in categories 4, 6 and 7 were indicative of orchestrated responses of different suites of genes in SUS or RES snails following exposure to Sm.


1995 ◽  
Vol 14 (1) ◽  
pp. 12-16
Author(s):  
K. N. De Kock

First generation cohorts of 25 specimens each of parental populations of Biomphalaria pfeifferi from four different localities, were each exposed to three Schistosoma mansoni miracidia per snail at an age of four weeks. The effect on survival was evaluated by calculating the weekly per capita mortality rates and the mean life-expectancy of the exposed snails. No significant differences could be demonstrated between the per capita mortality rates of F₁ cohorts of the two parental strains originating from localities in endemic bilharzia areas. Likewise there were no significant differences in this respect as far as F₁ cohorts of the two strains originating from localities in non-endemic bilharzia areas were concerned.


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