Abstract
Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the closely linked B. microti genes annotated as BMR1_03g00947 and BMR1_03g00960 encode two paralogue pRAP-1-like proteins named BmIPA48 and Bm960. The two genes are tandemly arranged head to tail, highly expressed in blood stage parasites, syntenic to rap-1 genes of other piroplasmids, and share large portions of an almost identical ~225 bp sequence located in their 5′ putative regulatory regions. BmIPA48 and Bm960 proteins contain a N-terminal signal peptide, share very low sequence identity (<13%) with pRAP-1 from other species, and harbor one or more transmembrane domains. Diversification of the piroplasmid-confined prap-1 family is characterized by amplification of genes, protein domains, and a high sequence polymorphism. This suggests a functional involvement of pRAP-1 at the parasite-host interface, possibly in parasite adhesion, attachment, and/or evasion of the host immune defenses. Both BmIPA48 and Bm960 are recognized by antibodies in sera from humans infected with B. microti and might be promising candidates for developing novel serodiagnosis and vaccines.
Highlights
Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan piroplasmid parasites of vertebrates that invade and reproduce asexually in erythrocytes
Because of the relatively distant phylogenetic relationship of B. microti with piroplasmid parasites such as Babesia s.s. and Theileria s.s. [1], we propose that the piroplasmid rhoptryassociated protein-1 (pRAP-1)-like proteins encoded by B. microti may have diverged dramatically from the pRAP-1 molecules expressed in other piroplasmids, resulting in a low non-significant sequence identity, but conservation of important structural features
Findings in this study suggest that rap-1 genes appeared early in the evolution of piroplasmid parasites, implying that expression of prap-1 and prap-1-like genes is required for sustaining the life cycle of these organisms
Summary
Cytauxzoon and Theileria are tick-borne apicomplexan piroplasmid parasites of vertebrates that invade and reproduce asexually in erythrocytes. These parasites are a major concern to human and animal health and cause an important economic burden worldwide. Babesia parasites are responsible for acute and persistent hemolytic disease in several wild and domestic vertebrate species, including human. While Theileria parasites are transmitted transstadially by ticks, sensu stricto (s.s.) Babesia spp. are transovarially and, in some species, transstadially, transmitted Other piroplasmids, such as B. microti, are defined as sensu lato (s.l.) Babesia parasites, based on their transstadial mode of transmission and the absence of schizont stages in their life cycles [1,2,3]. Because of the expansion of the tick habitat and the constant increase in cases of human babesiosis in the US, there is a need to develop vaccines and improved diagnostics against B. microti, which requires identification of conserved immunogenic proteins in this apicomplexan parasite
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