Adult Male Parasites Research Articles

Onchocerciasis Drug Discovery: In Vitro Evaluation of FDA-Approved Drugs against Onchocerca gutturosa in Gambia.

Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of Onchocerca volvulus but limited activity against the long-lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination, there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study, we have examined the anti-Onchocerca activity of a range of existing FDA-approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against O. gutturosa adult male parasites using a concentration of 1.25 × 10-5 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate and rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti-Onchocerca drug candidates worthy of further investigation.

A chromosome-level genome of the human blood fluke Schistosoma japonicum identifies the genomic basis of host-switching.

The evolution and adaptation of S.japonicum, a zoonotic parasite that causes human schistosomiasis, remain unclear because of the lack of whole-genome data. We construct a chromosome-level S.japonicum genome and analyze it together with 72 samples representing six populations of the entire endemic region. We observe a Taiwan zoophilic lineage splitting from zoonotic populations ∼45,000 years ago, consistent with the divergent history of their intermediate hosts. Interestingly, we detect a severe population bottleneck in S.japonicum, largely coinciding with human history in Asia during the last glacial maximum. We identify several genomic regions underlying natural selection, including GATAD2A and Lmln, both showing remarkable differentiation among different areas. RNAi knockdown suggests association of GATAD2A with parasite development and infection in definitive hosts, while Lmln relates to the specificity of the intermediate hosts. Our study provides insights into the evolution of S.japonicum and serves as a resource for further studies.

Is there a sex-specific difference between parasitic chicks in begging behaviour?

Offspring of birds and mammals demand food from their parents through an array of movements and vocalisations known collectively as begging behaviour. We explored sex-specific differences in the begging behaviour of a brood parasite, the common cuckoo (Cuculus canorus), fostered by the great reed warbler (Acrocephalus arundinaceus). As adult male parasites are larger than female parasites, we predicted that male chicks would vocalise more than female chicks. We also predicted a higher frequency of pecking in male chicks than female chicks, and in older compared to younger chicks. Pecking was considered to be any sudden attack of the parasite directed at the head or body of the hosts. Our observations confirmed that there were no sex-specific differences in nestling begging vocalisation and that older chicks tended to deliver more pecks at their hosts than younger ones. One explanation for the lack of intersexual differences in begging vocalisation is that the common cuckoo is an evictor parasite which does not need to compete for food. Alternatively, both male and female cuckoos might already beg at their maximum intensity or have similar food requirements. Moreover, the pecking behaviour in older nestlings could be a strategy to obtain more food from hosts without increasing host-present begging vocalisation.

The identification, expression profile, and preliminary characterization of Tsunagi protein from Schistosoma japonicum

Tsunagi is an evolutionarily conserved protein, which is required for germ line differentiation during the development of Drosophila melanogaster and Caenorhabditis elegans. In this paper, we describe a homologue of the Tsunagi protein from Schistosoma japonicum (SjTsunagi). The gene for this protein was isolated from S. japonicum using degenerate and anchored polymerase chain reaction (PCR), and the deduced protein has sequence homology and similarity to Tsunagi protein of other species, including C. elegans, D. melanogaster, Xenopus laevis, Mus musculus, and human. Amino acid sequence analysis showed the presence of a conserved RNA recognition motif. The predicted protein encoded by SjTsunagi gene is 177 amino acids in length with an estimated molecular mass of 20 kD. Immunoblot and reverse transcription-PCR analysis confirms SjTsunagi protein is expressed in eggs, cercariae, schistosomula, and adult female and adult male parasites. Pull-down and co-immunoprecipitation assay confirms that protein of SjTsunagi can interact with SjMago nashi in vitro. Taken together, this is the first report of the expression and preliminary characterization analysis of the SjTsunagi gene from S. japonicum.

Molecular characterization and real-time PCR transcriptional analysis of Dictyocaulus viviparus major sperm proteins

Major sperm proteins (MSPs) represent a protein family occurring in nematodes only. Identification of the 3' and 5' untranslated region (UTR) completed the so far partial msp complementary DNA sequences of the bovine lungworm Dictyocaulus viviparus. The full-length transcript contains sequence tracts consistent with the Kozak and polyadenylation consensus sequence. On genomic level, three full-length sequences differing in three nucleotides were determined containing a 65-bp phase zero intron. Conceptual translation inferred two MSP isoforms due to one substitution within the 126-amino acid polypeptide. Bioinformatic analysis predicted that bovine lungworm MSP folds into an immunoglobulin-like seven-stranded beta sandwich as known for Caenorhabditis elegans and Ascaris suum. Furthermore, bovine lungworm MSP is confidentially predicted to be N-terminal-acetylated and secreted via a non-classical pathway. Quantitative real-time polymerase chain reaction analysis using ten developmental lungworm stages showed that msp is transcribed mainly in adult male parasites and in some degree in hypobiotic L5. However, marginal msp transcription was detectable in all of the investigated developmental lungworm stages.

A bone morphogenetic protein homologue in the parasitic flatworm, Schistosoma mansoni

Members of the bone morphogenetic protein (BMP) subfamily of cytokines control many aspects of metazoan development including patterning and organogenesis. Despite the recognition that schistosomes possess key components of a BMP signaling pathway, a BMP-like ligand in the parasitic flatworm Schistosoma mansoni remained elusive. Here, we describe the cloning and characterisation of an S. mansoni BMP ( SmBMP). SmBMP is most closely related to BMP homologues from the free-living flatworms Schmidtea mediterranea and Dugesia japonica, with 51% and 47% identity at the amino acid level, respectively. Based on reverse transcription-PCR, SmBMP is expressed throughout the mammalian life-cycle of the parasite in both male and female schistosomes. In support of these results, antibodies to SmBMP successfully immunoprecipitated the protein in adult male and female antigen preparations with more protein detected in male parasites. Immunofluorescent studies localised SmBMP to the protonephridia of adult parasites, and SmBMP was identified in the excretory/secretory products of adult male parasites via immunoprecipitation. With the previous description of a TGF-β subfamily homologue in S. mansoni, ligands representing both arms of the TGF-β superfamily have now been described in this trematode.

Schistosoma mansoni: Demonstration of Homospecific Antibody Adsorbed to the Tegumental Surfaces of Adult Male Parasites from Mice

is a well-documented phenomenon and has been suggested as a possible means of immune escape (Smithers et al., 1969, Proceedings of the Royal Society of London [Biology] 171: 483-494). Among those host antigens consistently found associated with the dorsal tegumental surfaces of adult Schistosoma mansoni are immunoglobulins (Sogandares-Bernal, 1976, Journal of Parasitology 62: 222-226; Kemp et al., 1976, Journal of Parasitology 62: 413-419) of the classes IgGI, IgG2a, IgG2b, IgG3, IgA, and IgM (Kemp et al., 1978, Experimental Parasitology 45: 8187). It has been further demonstrated that a considerable number of these immunoglobulins are specific for antigens other than the parasite (heterospecific antibody), that they are oriented on the tegument in such a manner that they are capable of binding their respective antigens (Kemp et al., 1977, Journal of Immunology 119: 1849-1854), and that some, if not all, of the IgG molecules present are bound to tegument membrane-associated Fc receptors (Tarleton and Kemp, 1981, Journal of Immunology 126: 379384). In order to further test the working hypothesis that adult male schistosomes adsorb characteristic samples of circulating antibodies to their tegumental surfaces via their Fc fragments, the present study was initiated to assay for the possible presence of homospecific (antischistosome) antibody on the tegumental surfaces of adult male worms and to ascertain their molecular orientation.

Host-finding Ability of Bracon hebetor and Its Influence upon Adult Parasite Survival and Fecundity 1

In laboratory studies the parasite-host interaction between Bracon hebetor Say and Ephestia cautella (Walker) was influenced by migration of host larvae prior to pupation and by parasite females feeding on hosts. Wandering host larvae were attacked 10 times more often than confined hosts. Adult female parasites often paralyze host without oviposition. Survival and fecundity of adult female parasites were directly related to the frequency of host-finding. Host-feeding prolonged adult female parasite survival, but adult male parasites did not host-feed. The effects of starvation were partially reversible when adult female parasites given host at 2- or 5-day intervals were again given host daily. The long reproductive life, short generation time, and reliance upon host as food for adults and offspring should make B. hebetor quite responsive to manipulation of host availability.