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

Abstract

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

The Complexity of Piroplasms Life Cycles

“…It is generally assumed that sexual commitment of Theileria is identical to Babesia and gametocytes occur in the circulating blood (Mehlhorn and Shein, 1984 ; Mehlhorn and Schein, 1993 ; Zapf and Schein, 1994b ; Gauer et al, 1995 ; Shaw, 2003 ; Bishop et al, 2004 ; Uilenberg, 2006 ). This is supported by recent descriptions of genes with expression specific to sexual commitment in intra-erythrocytic stages of Theileria sensu stricto species (Pieszko et al, 2015 ; Lempereur et al, 2017 ) and T. equi (Bastos et al, 2013 ). The gametocytes are taken up into the tick midgut together with the blood meal.…”

The diversity of uncharacterized antibiotic resistance genes can be predicted from known gene variants—but not always

“…Moreover, metagenomic sequencing enables reanalysis of sequence data for new resistance genes discovered after the samples were initially analyzed [ 51 , 52 ], enabling retrospective analysis of monitoring data. An additional benefit of utilizing metagenomic sequencing over qPCR arrays is the possibility to computationally predict novel resistance genes from sequence data [ 53 , 54 ], although this specific practice is quite unlikely to be employed as part of monitoring schemes.…”

Pursuing effective vaccines against cattle diseases caused by apicomplexan protozoa

“…Another recent study used in silico analysis combined with gene expression in tick stages of the parasite to identify T. annulata candidate antigens for a transmissionblocking vaccine. By searching the T. annulata genome for amino acid domains on similar transmission-blocking sexual-stage targets from Plasmodium and Babesia parasites, this study identified candidates encoding the 6-cys and cysteine-rich domain protein families [39]. Vaccine trials in cattle are needed to test these newly identified vaccine candidates in their efficiency to block T. annulata transmission.…”

“…and Theileria spp. [39,101,105,106] and have been shown to be effective in reducing transmission upon vaccination in different models [107]. Antigens differentially expressed in kinete stages are also possible candidates for developing TBV.…”