Novel Babesia bovis exported proteins that modify properties of infected red blood cells.

Hassan Hakimi,Masahito Asada,Osamu Kaneko,Junya Yamagishi,Miako Sakaguchi,Thomas J Templeton,Kazuhide Yahata,Takayuki Uchihashi,Shinya Miyazaki,Shin-Ichiro Kawazu

doi:10.1371/journal.ppat.1008917

Abstract

Babesia bovis causes a pathogenic form of babesiosis in cattle. Following invasion of red blood cells (RBCs) the parasite extensively modifies host cell structural and mechanical properties via the export of numerous proteins. Despite their crucial role in virulence and pathogenesis, such proteins have not been comprehensively characterized in B. bovis. Here we describe the surface biotinylation of infected RBCs (iRBCs), followed by proteomic analysis. We describe a multigene family (mtm) that encodes predicted multi-transmembrane integral membrane proteins which are exported and expressed on the surface of iRBCs. One mtm gene was downregulated in blasticidin-S (BS) resistant parasites, suggesting an association with BS uptake. Induced knockdown of a novel exported protein encoded by BBOV_III004280, named VESA export-associated protein (BbVEAP), resulted in a decreased growth rate, reduced RBC surface ridge numbers, mis-localized VESA1, and abrogated cytoadhesion to endothelial cells, suggesting that BbVEAP is a novel virulence factor for B. bovis.

Highlights

Babesiosis is an emerging tick-borne disease affecting animals and humans which is caused by intraerythrocytic protozoans of the genus Babesia
Our knowledge of Babesia surface exposed proteins is limited to variant erythrocyte surface antigen1 (VESA1), which is responsible for fatal cerebral babesiosis
While pathogenesis of B. bigemina is mainly related to intravascular hemolysis, sequestration of B. bovis-infected red blood cells in internal organs and brain produces severe clinical symptoms which occasionally result in fatality [1]

Summary

Introduction

Babesiosis is an emerging tick-borne disease affecting animals and humans which is caused by intraerythrocytic protozoans of the genus Babesia. The burden of bovine babesiosis in tropical and subtropical regions is attributed to Babesia bovis and Babesia bigemina. While pathogenesis of B. bigemina is mainly related to intravascular hemolysis, sequestration of B. bovis-infected red blood cells (iRBCs) in internal organs and brain produces severe clinical symptoms which occasionally result in fatality [1]. Constraints against disease control include the low efficacy of available live vaccines for B. bovis, limited treatment options, and the emergence of drug and acaricide resistance of tick vectors [1,2,3]. The combination of new drugs and vaccine intervention are required to better control the disease

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