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      Identification of candidate transmission-blocking antigen genes in Theileria annulata and related vector-borne apicomplexan parasites

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          Abstract

          Background

          Vector-borne apicomplexan parasites are a major cause of mortality and morbidity to humans and livestock globally. The most important disease syndromes caused by these parasites are malaria, babesiosis and theileriosis. Strategies for control often target parasite stages in the mammalian host that cause disease, but this can result in reservoir infections that promote pathogen transmission and generate economic loss. Optimal control strategies should protect against clinical disease, block transmission and be applicable across related genera of parasites. We have used bioinformatics and transcriptomics to screen for transmission-blocking candidate antigens in the tick-borne apicomplexan parasite, Theileria annulata.

          Results

          A number of candidate antigen genes were identified which encoded amino acid domains that are conserved across vector-borne Apicomplexa ( Babesia, Plasmodium and Theileria), including the Pfs48/45 6-cys domain and a novel cysteine-rich domain. Expression profiling confirmed that selected candidate genes are expressed by life cycle stages within infected ticks. Additionally, putative B cell epitopes were identified in the T. annulata gene sequences encoding the 6-cys and cysteine rich domains, in a gene encoding a putative papain-family cysteine peptidase, with similarity to the Plasmodium SERA family, and the gene encoding the T. annulata major merozoite/piroplasm surface antigen, Tams1.

          Conclusions

          Candidate genes were identified that encode proteins with similarity to known transmission blocking candidates in related parasites, while one is a novel candidate conserved across vector-borne apicomplexans and has a potential role in the sexual phase of the life cycle. The results indicate that a ‘One Health’ approach could be utilised to develop a transmission-blocking strategy effective against vector-borne apicomplexan parasites of animals and humans.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12864-017-3788-1) contains supplementary material, which is available to authorized users.

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          Most cited references45

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          Improved method for predicting linear B-cell epitopes

          Background B-cell epitopes are the sites of molecules that are recognized by antibodies of the immune system. Knowledge of B-cell epitopes may be used in the design of vaccines and diagnostics tests. It is therefore of interest to develop improved methods for predicting B-cell epitopes. In this paper, we describe an improved method for predicting linear B-cell epitopes. Results In order to do this, three data sets of linear B-cell epitope annotated proteins were constructed. A data set was collected from the literature, another data set was extracted from the AntiJen database and a data sets of epitopes in the proteins of HIV was collected from the Los Alamos HIV database. An unbiased validation of the methods was made by testing on data sets on which they were neither trained nor optimized on. We have measured the performance in a non-parametric way by constructing ROC-curves. Conclusion The best single method for predicting linear B-cell epitopes is the hidden Markov model. Combining the hidden Markov model with one of the best propensity scale methods, we obtained the BepiPred method. When tested on the validation data set this method performs significantly better than any of the other methods tested. The server and data sets are publicly available at .
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            A central role for P48/45 in malaria parasite male gamete fertility.

            Fertilization and zygote development are obligate features of the malaria parasite life cycle and occur during parasite transmission to mosquitoes. The surface protein PFS48/45 is expressed by male and female gametes of Plasmodium falciparum and PFS48/45 antibodies prevent zygote development and transmission. Here, gene disruption was used to show that Pfs48/45 and the ortholog Pbs48/45 from a rodent malaria parasite P. berghei play a conserved and important role in fertilization. p48/45- parasites had a reduced capacity to produce oocysts in mosquitoes due to greatly reduced zygote formation. Unexpectedly, only male gamete fertility of p48/45- parasites was affected, failing to penetrate otherwise fertile female gametes. P48/45 is shown to be a surface protein of malaria parasites with a demonstrable role in fertilization.
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              A photosynthetic alveolate closely related to apicomplexan parasites.

              Many parasitic Apicomplexa, such as Plasmodium falciparum, contain an unpigmented chloroplast remnant termed the apicoplast, which is a target for malaria treatment. However, no close relative of apicomplexans with a functional photosynthetic plastid has yet been described. Here we describe a newly cultured organism that has ultrastructural features typical for alveolates, is phylogenetically related to apicomplexans, and contains a photosynthetic plastid. The plastid is surrounded by four membranes, is pigmented by chlorophyll a, and uses the codon UGA to encode tryptophan in the psbA gene. This genetic feature has been found only in coccidian apicoplasts and various mitochondria. The UGA-Trp codon and phylogenies of plastid and nuclear ribosomal RNA genes indicate that the organism is the closest known photosynthetic relative to apicomplexan parasites and that its plastid shares an origin with the apicoplasts. The discovery of this organism provides a powerful model with which to study the evolution of parasitism in Apicomplexa.
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                Author and article information

                Contributors
                llempereur@ulg.ac.be
                Stephen.larcombe@glasgow.ac.uk
                Z.Durrani@liverpool.ac.uk
                tulinkaragenc@yahoo.com
                huseyin_bilgic@yahoo.com
                serkanbakirci@adu.edu.tr
                selin-uner@hotmail.com
                jane.kinnaird@glasgow.ac.uk
                Joanne.Thompson@ed.ac.uk
                willie.weir@glasgow.ac.uk
                brian.shiels@glasgow.ac.uk
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                5 June 2017
                5 June 2017
                2017
                : 18
                : 438
                Affiliations
                [1 ]ISNI 0000 0001 2193 314X, GRID grid.8756.c, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary & Life Sciences, , University of Glasgow, ; 464 Bearsden Road, Glasgow, G61 1QH Scotland UK
                [2 ]ISNI 0000 0001 0805 7253, GRID grid.4861.b, Present address: Laboratory of Parasitology and Parasitic Diseases, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, , University of Liège, ; Liège, Belgium
                [3 ]ISNI 0000 0004 1936 8470, GRID grid.10025.36, Present address: School of Veterinary Science, , University of Liverpool, ; Chester High Road, Neston, CH64 7TE, UK
                [4 ]ISNI 0000 0004 0595 4313, GRID grid.34517.34, Faculty of Veterinary Medicine, Department of Parasitology, , Adnan Menderes University, ; Batı Kampus, Işıklı, Aydın Turkey
                [5 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, Institute of Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, , University of Edinburgh, ; The King’s Buildings, Edinburgh, EH9 3FL UK
                Article
                3788
                10.1186/s12864-017-3788-1
                5460460
                e64ab0a5-027f-4934-bbbb-0541d30000a0
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 January 2017
                : 11 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000268, Biotechnology and Biological Sciences Research Council;
                Award ID: BB/L004739/1
                Award Recipient :
                Funded by: EU
                Award ID: 238511
                Award Recipient :
                Funded by: TUBITAK
                Award ID: 111O718
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Genetics
                theileria annulata,plasmodium,babesia,bioinformatic screen,transmission-blocking vaccine,6-cys domain

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