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

Mol Biochem Parasitol. 2004 Aug;136(2):165-72. doi: 10.1016/j.molbiopara.2004.03.009.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan
  • Babesia bovis / drug effects*
  • Babesia bovis / enzymology*
  • Babesia bovis / genetics
  • Babesia bovis / growth & development
  • Babesiosis / drug therapy
  • Babesiosis / parasitology
  • Babesiosis / veterinary*
  • Cattle
  • Cattle Diseases / drug therapy*
  • Cattle Diseases / parasitology
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA, Protozoan / genetics
  • Enzyme Inhibitors / pharmacology
  • Female
  • Genes, Protozoan
  • Gossypol / pharmacology
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / genetics*
  • L-Lactate Dehydrogenase / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data

Substances

  • Antibodies, Protozoan
  • DNA, Complementary
  • DNA, Protozoan
  • Enzyme Inhibitors
  • L-Lactate Dehydrogenase
  • Gossypol

Associated data

  • GENBANK/AB112429