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

Hakimi, Hassan; Templeton, Thomas J.; Sakaguchi, Minoru; Yamagishi, Junya; Miyazaki, Shuichi; Yahata, Kazuhide; Uchihashi, Takayuki; Kawazu, Shin-ichiro; Kaneko, O.; Asada, Masahito

doi:10.1371/journal.ppat.1008917

Cited by 18 publications

(80 citation statements)

References 62 publications

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“…These relatives of Plasmodium also infect erythrocytes but destroy the PVM moments after invasion [ 181 ], enabling protein secretion directly into the iRBC. While this obviates the need for a PVM translocon, Babesia exported effectors still contain a PEXEL-like motif which may mediate their packaging and release from secretory organelles [ 182 , 183 ].…”

Section: Perspectives and Future Questionsmentioning

confidence: 99%

Transport mechanisms at the malaria parasite-host cell interface

Beck

2021

PLoS Pathog

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Obligate intracellular malaria parasites reside within a vacuolar compartment generated during invasion which is the principal interface between pathogen and host. To subvert their host cell and support their metabolism, these parasites coordinate a range of transport activities at this membrane interface that are critically important to parasite survival and virulence, including nutrient import, waste efflux, effector protein export, and uptake of host cell cytosol. Here, we review our current understanding of the transport mechanisms acting at the malaria parasite vacuole during the blood and liver-stages of development with a particular focus on recent advances in our understanding of effector protein translocation into the host cell by the Plasmodium Translocon of EXported proteins (PTEX) and small molecule transport by the PTEX membrane-spanning pore EXP2. Comparison to Toxoplasma gondii and other related apicomplexans is provided to highlight how similar and divergent mechanisms are employed to fulfill analogous transport activities.

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Section: Perspectives and Future Questionsmentioning

confidence: 99%

Transport mechanisms at the malaria parasite-host cell interface

Beck

2021

PLoS Pathog

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“…This protein has been shown to be secreted from micronemes during the intraerythrocytic parasite stage and bind to the pRBC membrane, where it facilitates the egress of the parasite [62]. A high-scoring protein named 'membrane, putative' (BBOV_III004280) has been experimentally verified in a recent study [60] to be an exported protein and a novel virulence factor for B. bovis.…”

Section: Full Babesia Bovis T2bo Exportome Predictionmentioning

confidence: 99%

“…Based on current knowledge, smORF and SBP2 are considered here as worthy exportome members. SBP2 proteins are shown to be released from spherical bodies following invasion and are believed to be responsible for RBC modifications [31,60,61]. SmORF proteins are known exported proteins that are proposed to play a role in variant erythrocyte surface antigen (VESA) protein biology [6], i.e., smORFs could assist in sequestration together with VESA1 proteins.…”

Section: Full Babesia Bovis T2bo Exportome Predictionmentioning

confidence: 99%

Applying Machine Learning to Predict the Exportome of Bovine and Canine Babesia Species That Cause Babesiosis

2021

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Babesia infection of red blood cells can cause a severe disease called babesiosis in susceptible hosts. Bovine babesiosis causes global economic loss to the beef and dairy cattle industries, and canine babesiosis is considered a clinically significant disease. Potential therapeutic targets against bovine and canine babesiosis include members of the exportome, i.e., those proteins exported from the parasite into the host red blood cell. We developed three machine learning-derived methods (two novel and one adapted) to predict for every known Babesia bovis, Babesia bigemina, and Babesia canis protein the probability of being an exportome member. Two well-studied apicomplexan-related species, Plasmodium falciparum and Toxoplasma gondii, with extensive experimental evidence on their exportome or excreted/secreted proteins were used as important benchmarks for the three methods. Based on 10-fold cross validation and multiple train–validation–test splits of training data, we expect that over 90% of the predicted probabilities accurately provide a secretory or non-secretory indicator. Only laboratory testing can verify that predicted high exportome membership probabilities are creditable exportome indicators. However, the presented methods at least provide those proteins most worthy of laboratory validation and will ultimately save time and money.

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“…Additionally, conditional knockdown of BbVEAP reduced B. bovis growth suggesting an important role of this protein for parasite development 8 . To investigate whether this growth defect is due to decreased invasion and/or parasite development in the RBC, we used bbveap glmS-myc tagged parasites 8 . The parasites were treated with 5 mM of Glucosamine (GlcN) for 24 h, merozoites were purified, invasion assay was performed, and parasites growth was monitored for 24 h post invasion (Fig.…”

Section: Induced Knockdown Of Bbveap Did Not Affect Rbc Invasion But mentioning

confidence: 99%

“…In order to study parasite developmental stages such as egress or invasion which happens within minutes, it is needed to artificially induce synchrony in the culture. Babesia parasites increase RBC permeability and change its density that could be used for enrichment and purification of infected RBCs (iRBCs) using percol-sorbitol or Histodenz density gradient centrifugation 7,8 . However, given that the parasite's erythrocytic cycle is quite short (1-2 cycles per day for B. bovis), it is impossible to separate ring from binary forms using these techniques.…”

Section: Introductionmentioning

confidence: 99%

Isolation of viable Babesia bovis merozoites to study parasite invasion

Hakimi

Asada

Ishizaki

et al. 2021

Preprint

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Babesia parasite invades exclusively red blood cell (RBC) in mammalian host and induce alterations to host cell for survival. Despite the importance of Babesia in livestock industry and emerging cases in humans, their basic biology is hampered by lack of suitable biological tools. In this study, we aimed to develop a synchronization method for Babesia bovis which causes the most pathogenic form of bovine babesiosis. Initially, we used compound 2 (C2), a specific inhibitor of cyclic GMP-dependent protein kinase (PKG) and a derivative of C2, ML10. While both inhibitors were able to prevent B. bovis egress from RBC and increased percentage of binary forms, removal of inhibitors from culture did not result in a synchronized egress of parasites. Because using PKG inhibitors alone was not efficient to induce a synchronized culture, we isolated viable and invasive B. bovis merozoites and showed dynamics of merozoite invasion and development in RBCs. Using isolated merozoites we showed that BbVEAP, VESA1-export associated protein, is essential for parasite development in the RBC while has no role in invasion. Given the importance of invasion for establishment of infection, this study paves the way for finding novel antigens to be used in control strategies against bovine babesiosis.

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

Cited by 18 publications

References 62 publications

Transport mechanisms at the malaria parasite-host cell interface

Transport mechanisms at the malaria parasite-host cell interface

Applying Machine Learning to Predict the Exportome of Bovine and Canine Babesia Species That Cause Babesiosis

Isolation of viable Babesia bovis merozoites to study parasite invasion

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