Sabine Bork

Laboratoire National de Santé

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Ikuo Igarashi

Obihiro University of Agriculture and Veterinary Medicine

Naoaki Yokoyama

Obihiro University of Agriculture and Veterinary Medicine

Masashi Okamura

Obihiro University of Agriculture and Veterinary Medicine

Tomohide Matsuo

Kagoshima University

Kozo Fujisaki

Obihiro University of Agriculture and Veterinary Medicine

Florencia G. Claveria

De La Salle University

Haruyuki Hirata

Rakuno Gakuen University

Noriyuki Takabatake

Obihiro University of Agriculture and Veterinary Medicine

Xuenan Xuan

Obihiro University of Agriculture and Veterinary Medicine

Chihiro Sugimoto

Hokkaido University

Cooperative Institutions

Obihiro University of Agriculture and Veterinary Medicine

The University of Tokyo

Qinghai University

Laboratoire National de Santé

University of Sadat City

Chinese Academy of Agricultural Sciences

Gifu University

De La Salle University

Luxembourg Institute of Health

Institut Pasteur du Laos

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Effects of protein kinase inhibitors on thein vitrogrowth ofBabesia bovis

Parasitology (2006)

Sabine Bork Sukta Das Kazuhiro Okubo Naoaki Yokoyama Ikuo Igarashi

Staurosporine, Ro-31-7549, and KN-93, which are inhibitors of serine/threonine protein kinase, protein kinase C, and calcium-modulin kinase, respectively, were tested for their effects on the in vitro growth of Babesia bovis . Staurosporine was the most effective inhibitor, completely clearing the parasitaemia as early as the first day of exposure at a concentration of 100 μ M . Moreover, staurosporine caused a significant increase in the percentage of extracellular merozoites, most likely due to the inhibition of erythrocyte invasion by the parasite. Although 5 m M Ro-31-7549 and KN-93 had a suppressive action, this was not enough to destroy the parasite. Interestingly, concentrations of 0·5 to 5 m M KN-93 influenced the parasitic development within the infected erythrocytes. The present study suggests that B. bovis requires, to a certain extent, the phosphorylations mediated by parasite- or host erythrocyte-protein kinases, in particular, for the processes of successful invasion of erythrocytes and intraerythrocytic development.

Staurosporine

Babesia bovis

10.1017/s0031182006009917

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Citations (17)

Growth-Inhibitory Effects of Artesunate, Pyrimethamine, and Pamaquine against Babesia equi and Babesia caballi in In Vitro Cultures

Antimicrobial Agents and Chemotherapy (2003)

Akiko Nagai Naoaki Yokoyama Tomohide Matsuo Sabine Bork Haruyuki Hirata

Three antimalarial drugs, artesunate, pyrimethamine, and pamaquine, were evaluated for their growth-inhibitory effects against Babesia equi and Babesia caballi in in vitro culture. B. equi was more resistant to pyrimethamine than B. caballi. B. equi was also found to be more sensitive to artesunate and pamaquine than B. caballi. Of the three compounds, pyrimethamine gave the most promise for in vivo effectiveness.

Artesunate

10.1128/aac.47.2.800-803.2003

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Roles of the Maltese Cross Form in the Development of Parasitemia and Protection against Babesia microti Infection in Mice

Infection and Immunity (2002)

Naoaki Yokoyama Sabine Bork Mitsuhiro Nishisaka Haruyuki Hirata Tomohide Matsuo

Babesia microti, a hemoprotozoan parasite of rodents, is also important as a zoonotic agent of human babesiosis. The Maltese cross form, which consists of four masses in an erythrocyte, is characteristic of the developmental stage of B. microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the Maltese cross form of B. microti, has been described previously. In the present study, we examined the roles of the Maltese cross form during the infectious course of B. microti in mice. The number of the Maltese cross form increased in the peripheral blood of infected mice prior to the peak of parasitemia. With confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the ring form, with the parasites undergoing transformation to the Maltese cross form and subsequent division, and also with extracellular merozoites. Furthermore, the Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA library by immunoscreening with MAb 2-1E, and the nucleotide sequence was determined. Genomic analyses indicated that the MRA gene exists as a single-copy gene in B. microti. Immunization of mice with recombinant MRA induced significant protective immunity against B. microti infection. These findings indicate that the Maltese cross form plays important roles in both the development of parasitemia and the protective response against the infection.

Maltese

10.1128/iai.71.1.411-417.2003

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Citations (27)

GROWTH INHIBITORY EFFECT OF TRICLOSAN ON EQUINE AND BOVINE BABESIA PARASITES

American Journal of Tropical Medicine and Hygiene (2003)

Sabine Bork Naoaki Yokoyama Tomohide Matsuo Florencia G. Claveria Kozo Fujisaki

We evaluated the growth inhibitory effect of triclosan, which has recently been reported to inhibit the growth of Plasmodium species and Toxoplasma gondii, on bovine and equine Babesia parasites in in vitro cultures The growth of Babesia bovis and B. bigemina was significantly inhibited in the presence of 100 microg/ml of triclosan, while B. caballi and B. equi were susceptible to as low as 50 microg/ml. Babesia bigemina and B. caballi were completely cleared as early as on the first and second day of the treatment, respectively. These parasites did not exhibit any growth in the subsequent five-day period of subculture without triclosan. Drug-treated parasites appeared pycnotic and atypically shaped, and ultrastructurally showed pronounced vacuolations, leading to complete destruction of parasites. Light microscopy showed that used concentrations of triclosan showed no toxicity against the host cells. The results suggest that triclosan can be used for chemotherapy of babesiosis.

Babesia bigemina

10.4269/ajtmh.2003.68.334

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Citations (65)

Clotrimazole, ketoconazole, and clodinafop-propargyl inhibit the in vitro growth of Babesia bigemina and Babesia bovis (Phylum Apicomplexa)

Parasitology (2003)

Sabine Bork Naoaki Yokoyama Tomohide Matsuo Florencia G. Claveria Kozo Fujisaki

We evaluated the growth inhibitory efficacy of the imidazole derivatives, clotrimazole (CLT) and ketoconazole (KC), and the herbicide clodinafop-propargyl (CP), in in vitro cultures of Babesia bovis and B. bigemina . Clotrimazole was effective in a dose range of 15 to 60 μ M (IC 50 : 11 and 23·5 μ M ), followed by KC (50 to 100 μ M ; IC 50 : 50 and 32 μ M ) and CP (500 μ M ; IC 50 : 265 and 390 μ M ). In transmission electron microscopy, extensive damage was observed in the cytoplasm of drug-treated parasites. Combinations of CLT/KC, CLT/CP and CLT/KC/CP acted synergistically in both parasites. In contrast, the combination of KC/CP was exclusively effective in B. bovis , but not in B. bigemina .

Babesia bigemina

Babesia bovis

Clotrimazole

10.1017/s0031182003003895

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Citations (27)

Challenges of measles and rubella laboratory diagnostic in the era of elimination

Clinical Microbiology and Infection (2017)

Judith M. Hübschen Sabine Bork Kevin Brown Annette Mankertz Scott Santibañez

Rubella virus

10.1016/j.cmi.2017.04.009

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Citations (81)

In vitro growth inhibitory effects of combined applications of clotrimazole, ketoconazole, and clodinafop-propargyl on equine Babesia parasites

Journal of protozoology research (2003)

Sabine Bork Naoaki Yokoyama Masashi Okamura Ikuo Igarashi 直明横山

Clotrimazole

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FUCOIDAN INHIBITS THE IN VITRO GROWTH OF BABESIA BOVIS

Journal of protozoology research (2004)

Noriyuki Takabatake Shintaro Hashiba Sabine Bork Masashi Okamura Naoaki Yokoyama

Babesia bovis

Fucoidan

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Citations (3)

Host serum modifies the drug susceptibility of Babesia bovis in vitro

Parasitology (2005)

Sabine Bork Masashi Okamura Tomohide Matsuo Sanjay Kumar Naoaki Yokoyama

Babesia parasites generally require a defined percentage of serum in the culture medium for their in vitro growth. In this study, we attempted to culture Babesia bovis in a serum-free condition. The growth pattern and morphology of B. bovis in serum-free (plain) GIT medium were unaltered as compared to those of the standard growth condition containing 40% bovine serum in M199. When exposed to the test drugs, the parasite in plain GIT medium showed clearly lower IC50 values than those in 40% serum-containing GIT medium, indicating that several serum components may interfere with the drug bio-availability. Therefore, the serum-free culture system is useful for standardizing drug test protocols and understanding the roles of serum factors in the drug test.

Babesia bovis

Babesia bigemina

10.1017/s0031182004006821

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Citations (34)

Identification of Babesia bovis l-lactate dehydrogenase as a potential chemotherapeutical target against bovine babesiosis

Molecular and Biochemical Parasitology (2004)

Sabine Bork Masashi Okamura Suthisak Boonchit Haruyuki Hirata Naoaki Yokoyama

Babesia bovis

Immunoscreening

10.1016/j.molbiopara.2004.03.009

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Citations (36)