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

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

doi:10.1371/journal.ppat.1008917

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

PLoS Pathog. 2020 Oct 5;16(10):e1008917. doi: 10.1371/journal.ppat.1008917. eCollection 2020 Oct.

Authors

Affiliations

¹ Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
² National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
³ Central Laboratory, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
⁴ Division of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
⁵ International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
⁶ Department of Physics, Nagoya University, Aichi, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Babesia bovis / genetics
Babesia bovis / pathogenicity*
Babesiosis / parasitology*
Cattle
Cattle Diseases / parasitology
Endothelial Cells / parasitology*
Erythrocytes / parasitology*
Membrane Proteins
Parasites / pathogenicity
Proteomics / methods
Virulence Factors / genetics

Substances

Membrane Proteins
Virulence Factors

Grants and funding

This study was supported partly by grants from Japan Society for the Promotion of Science (https://www.jsps.go.jp/english/) to H.H. (15K18783, 19K15983), M.A. (16K08021, 19K06384), S.K. (18K19258, 19H03120) and O.K. (16F16105). This work was supported by NRCPD OUAVM Joint Research Grant of NRCPD, Obihiro University of Agriculture and Veterinary Medicine (https://www.obihiro.ac.jp/facility/protozoa/ento) to M.A. (28-11, 29-2, 30-1). H.H. is a recipient of the JSPS Postdoctoral Fellowship for foreign researchers from the Japan Society for the Promotion of Science. T.J.T. was supported by a visiting professorship to the Institute of Tropical Medicine, Nagasaki University (http://www.tm.nagasaki-u.ac.jp/nekken/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.