Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors

Abstract Infections of dogs with virulent strains of Babesia canis are characterized by rapid onset and high mortality, comparable to complicated human malaria. As in other apicomplexan parasites, most Babesia virulence factors responsible for survival and pathogenicity are secreted to the host cell...

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Main Authors: Ramon M. Eichenberger, Chandra Ramakrishnan, Giancarlo Russo, Peter Deplazes, Adrian B. Hehl
Format: Article
Language:English
Published: Nature Portfolio 2017-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-03445-x
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author Ramon M. Eichenberger
Chandra Ramakrishnan
Giancarlo Russo
Peter Deplazes
Adrian B. Hehl
author_facet Ramon M. Eichenberger
Chandra Ramakrishnan
Giancarlo Russo
Peter Deplazes
Adrian B. Hehl
author_sort Ramon M. Eichenberger
collection DOAJ
description Abstract Infections of dogs with virulent strains of Babesia canis are characterized by rapid onset and high mortality, comparable to complicated human malaria. As in other apicomplexan parasites, most Babesia virulence factors responsible for survival and pathogenicity are secreted to the host cell surface and beyond where they remodel and biochemically modify the infected cell interacting with host proteins in a very specific manner. Here, we investigated factors secreted by B. canis during acute infections in dogs and report on in silico predictions and experimental analysis of the parasite’s exportome. As a backdrop, we generated a fully annotated B. canis genome sequence of a virulent Hungarian field isolate (strain BcH-CHIPZ) underpinned by extensive genome-wide RNA-seq analysis. We find evidence for conserved factors in apicomplexan hemoparasites involved in immune-evasion (e.g. VESA-protein family), proteins secreted across the iRBC membrane into the host bloodstream (e.g. SA- and Bc28 protein families), potential moonlighting proteins (e.g. profilin and histones), and uncharacterized antigens present during acute crisis in dogs. The combined data provides a first predicted and partially validated set of potential virulence factors exported during fatal infections, which can be exploited for urgently needed innovative intervention strategies aimed at facilitating diagnosis and management of canine babesiosis.
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spelling doaj.art-5fcd6610a27542b29bb14c772125917a2022-12-21T20:38:50ZengNature PortfolioScientific Reports2045-23222017-06-017111410.1038/s41598-017-03445-xGenome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factorsRamon M. Eichenberger0Chandra Ramakrishnan1Giancarlo Russo2Peter Deplazes3Adrian B. Hehl4Institute of Parasitology, University of ZurichInstitute of Parasitology, University of ZurichFunctional Genomics Center ZurichInstitute of Parasitology, University of ZurichInstitute of Parasitology, University of ZurichAbstract Infections of dogs with virulent strains of Babesia canis are characterized by rapid onset and high mortality, comparable to complicated human malaria. As in other apicomplexan parasites, most Babesia virulence factors responsible for survival and pathogenicity are secreted to the host cell surface and beyond where they remodel and biochemically modify the infected cell interacting with host proteins in a very specific manner. Here, we investigated factors secreted by B. canis during acute infections in dogs and report on in silico predictions and experimental analysis of the parasite’s exportome. As a backdrop, we generated a fully annotated B. canis genome sequence of a virulent Hungarian field isolate (strain BcH-CHIPZ) underpinned by extensive genome-wide RNA-seq analysis. We find evidence for conserved factors in apicomplexan hemoparasites involved in immune-evasion (e.g. VESA-protein family), proteins secreted across the iRBC membrane into the host bloodstream (e.g. SA- and Bc28 protein families), potential moonlighting proteins (e.g. profilin and histones), and uncharacterized antigens present during acute crisis in dogs. The combined data provides a first predicted and partially validated set of potential virulence factors exported during fatal infections, which can be exploited for urgently needed innovative intervention strategies aimed at facilitating diagnosis and management of canine babesiosis.https://doi.org/10.1038/s41598-017-03445-x
spellingShingle Ramon M. Eichenberger
Chandra Ramakrishnan
Giancarlo Russo
Peter Deplazes
Adrian B. Hehl
Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
Scientific Reports
title Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
title_full Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
title_fullStr Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
title_full_unstemmed Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
title_short Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors
title_sort genome wide analysis of gene expression and protein secretion of babesia canis during virulent infection identifies potential pathogenicity factors
url https://doi.org/10.1038/s41598-017-03445-x
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