Babesia bovis: a potential new immunotherapeutic target

GALLENTI ROMINA; POKLEPOVICH,TOMAS; FLORIN-CHRISTENSEN, M; SCHNITTGER, LEONHARD

Congreso; 9th Tick and Tick-borne Pathogen Conference & 1st Asia Pacific Rickettsia Conference; 2017

Rhomboid serine proteases (ROM) of type 4/5 ofApicomplexans cleave adhesins at the parasite membrane after their attachmentto host cell ligands. Their activity is needed to complete internalization intothe host cell, an essential step for parasite survival. As components ofvaccine formulations they were able to generate partial protection againstToxoplasma and Eimeria. Bioinformatic analysis showed an expansion of the ROM4/5 family in Babesia bovis (Texas strain T2Bo) comprising 5 compared to only 2or 3 paralogs in other piroplasmids and a single ortolog in Plasmodium falciparum.Given the importance of this gene family as potential therapeutic target in B.bovis further studies were carried out. ROM4/5 paralogs are encoded in a regionof chromosome II where several other protease-encoding genes are located. Threeof them (here named ROM 4.1, ROM 4.2, and ROM 4.3) are organized head to tailin tandem and likely arose after two duplication events. PCR ampliconsequencing of these genes from the Argentine R1A strain showed somepolymorphism with respect to T2Bo in the region corresponding to the aminoterminus of ROM 4.1, while the remaining sequences are highly conserved. Asdescribed for other rhomboid serine proteases, B. bovis ROM 4.1, 4.2, and 4.3contain several transmembrane domains and a hydrophobic intramembrane catalyticsite. Their amino termini are soluble and extracellular. Several predicted Bcell epitopes are conserved between the two analyzed geographically distantisolates, providing potential targets for immunotherapeutic interventions.