Identification of Babesia bovis L-lactate dehydrogenase as a potential chemotherapeutical target against bovine babesiosis
| Autor: | Haruyuki Hirata, Sabine Bork, Masashi Okamura, Ikuo Igarashi, Naoaki Yokoyama, Suthisak Boonchit |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
DNA
Complementary Genes Protozoan Molecular Sequence Data Antibodies Protozoan Cattle Diseases In Vitro Techniques law.invention chemistry.chemical_compound Mice law Lactate dehydrogenase Immunoscreening Babesiosis parasitic diseases Animals Amino Acid Sequence Bovine serum albumin Cloning Molecular Enzyme Inhibitors Molecular Biology Mice Inbred BALB C biology L-Lactate Dehydrogenase Gossypol Toxoplasma gondii Babesia bovis Plasmodium falciparum DNA Protozoan biology.organism_classification Molecular biology chemistry Recombinant DNA biology.protein Parasitology Cattle Female |
| Zdroj: | Molecular and biochemical parasitology. 136(2) |
| ISSN: | 0166-6851 |
| Popis: | In this study, we characterized a novel Babesia bovis cDNA clone obtained by immunoscreening the cDNA expression phage library with B. bovis-infected bovine serum. The genetic analyses showed that it contained an open reading frame of 993 bp, which was considered to encode B. bovis L-lactate dehydrogenase (BbLDH: E.C. 1.1.1.27) because of the strikingly high amino acid identities of its gene product to the LDHs of Plasmodium falciparum and Toxoplasma gondii. Immunological analyses with the anti-recombinant BbLDH mouse serum showed that 36 kDa of the native BbLDH was expressed not only in the cytoplasm of intra- and extraerythrocytic parasites but also along the membrane of infected erythrocytes. The kinetic properties of recombinant BbLDH proved a certain enzymatic activity of LDH, and the activity was significantly inhibited by the addition of gossypol, a competitive inhibitor of protozoan LDHs. Moreover, 100 microM of the gossypol irretrievably arrested the in vitro growth of B. bovis. The results demonstrated that BbLDH provides a suitable drug target for the design of novel babesial chemotherapeutics. |
| Databáze: | OpenAIRE |
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