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

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 h...

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Main Authors: Hassan Hakimi, Thomas J Templeton, Miako Sakaguchi, Junya Yamagishi, Shinya Miyazaki, Kazuhide Yahata, Takayuki Uchihashi, Shin-Ichiro Kawazu, Osamu Kaneko, Masahito Asada
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-10-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1008917
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author Hassan Hakimi
Thomas J Templeton
Miako Sakaguchi
Junya Yamagishi
Shinya Miyazaki
Kazuhide Yahata
Takayuki Uchihashi
Shin-Ichiro Kawazu
Osamu Kaneko
Masahito Asada
author_facet Hassan Hakimi
Thomas J Templeton
Miako Sakaguchi
Junya Yamagishi
Shinya Miyazaki
Kazuhide Yahata
Takayuki Uchihashi
Shin-Ichiro Kawazu
Osamu Kaneko
Masahito Asada
author_sort Hassan Hakimi
collection DOAJ
description 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.
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spelling doaj.art-d1fbd54d54814d53921d7605c17486112022-12-21T19:11:10ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-10-011610e100891710.1371/journal.ppat.1008917Novel Babesia bovis exported proteins that modify properties of infected red blood cells.Hassan HakimiThomas J TempletonMiako SakaguchiJunya YamagishiShinya MiyazakiKazuhide YahataTakayuki UchihashiShin-Ichiro KawazuOsamu KanekoMasahito AsadaBabesia 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.https://doi.org/10.1371/journal.ppat.1008917
spellingShingle Hassan Hakimi
Thomas J Templeton
Miako Sakaguchi
Junya Yamagishi
Shinya Miyazaki
Kazuhide Yahata
Takayuki Uchihashi
Shin-Ichiro Kawazu
Osamu Kaneko
Masahito Asada
Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
PLoS Pathogens
title Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
title_full Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
title_fullStr Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
title_full_unstemmed Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
title_short Novel Babesia bovis exported proteins that modify properties of infected red blood cells.
title_sort novel babesia bovis exported proteins that modify properties of infected red blood cells
url https://doi.org/10.1371/journal.ppat.1008917
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