Abstract
Apicomplexan genomes encode multiple pepsin-family aspartyl proteases (APs) that phylogenetically cluster to six independent clades (A to F). Such diversification has been powered by the function-driven evolution of the ancestral apicomplexan AP gene and is associated with the adaptation of various apicomplexan species to different strategies of host infection and transmission through various invertebrate vectors. To estimate the potential roles of Babesia APs, we performed qRT-PCR-based expressional profiling of Babesia microti APs (BmASP2, 3, 5, 6), which revealed the dynamically changing mRNA levels and indicated the specific roles of individual BmASP isoenzymes throughout the life cycle of this parasite. To expand on the current knowledge on piroplasmid APs, we searched the EuPathDB and NCBI GenBank databases to identify and phylogenetically analyse the complete sets of APs encoded by the genomes of selected Babesia and Theileria species. Our results clearly determine the potential roles of identified APs by their phylogenetic relation to their homologues of known function—Plasmodium falciparum plasmepsins (PfPM I–X) and Toxoplasma gondii aspartyl proteases (TgASP1–7). Due to the analogies with plasmodial plasmepsins, piroplasmid APs represent valuable enzymatic targets that are druggable by small molecule inhibitors—candidate molecules for the yet-missing specific therapy for babesiosis.
Highlights
Babesiosis is a malaria-like disease caused by the parasites from the genus Babesia of the apicomplexan order Piroplasmida
As cell-traversal protein of ookinetes and sporozoites (CelTOS) is conserved among apicomplexan parasites [80], we propose that its processing by clade C aspartyl proteases (APs) plays an important role during the transmission of piroplasmid species through their tick vectors
TRAP is a conserved family of proteins that are involved in the gliding motility of apicomplexan parasites, and are found in Babesia [68,83]
Summary
Babesiosis ( known as piroplasmosis) is a malaria-like disease caused by the parasites from the genus Babesia of the apicomplexan order Piroplasmida This order was initially represented by three separated lineages—Babesia, Theileria, and Cytauxzoon—but more recent phylogenetic analyses have indicated approximately six lineages of Piroplasmida, out of which the approximately 100 Babesia species are represented in at least three distinct clades [1]. The multiple Apicomplexan APs are phylogenetically clustered into six clearly distinguishable clades, tagged A–F These clades reflect the function-driven evolution and various biological roles of these enzymes within the life cycle of these parasitic organisms [16,17]. Our estimation is supported by the dynamic expression profiling throughout selected life stages of Babesia microti using our previously developed B. microti–Ixodes ricinus–mouse acquisition model [20]
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