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An Eimeria vaccine candidate appears to be lactate dehydrogenase; characterization and comparative analysis

Published online by Cambridge University Press:  13 May 2004

D. SCHAAP ,
G. ARTS ,
J. KROEZE ,
R. NIESSEN ,
S. V. ROOSMALEN-VOS ,
K. SPREEUWENBERG ,
C. M. KUIPER ,
N. V. D. BEEK-VERHOEVEN ,
J. J. KOK  and
R. M. A. KNEGTEL
...Show all authors
D. SCHAAP
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
G. ARTS
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
J. KROEZE
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands Present address: Department of Parasitology, Leiden University Medical Centre, the Netherlands.
R. NIESSEN
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
S. V. ROOSMALEN-VOS
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
K. SPREEUWENBERG
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
C. M. KUIPER
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
N. V. D. BEEK-VERHOEVEN
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
J. J. KOK
Affiliation:
Target Discovery Unit, Organon, PO Box 20, 5340BH Oss, the Netherlands
R. M. A. KNEGTEL
Affiliation:
Target Discovery Unit, Organon, PO Box 20, 5340BH Oss, the Netherlands Present address: Vertex Pharmaceuticals (Europe) Ltd, 88 Milton Park, Abingdon, Oxfordshire, UK.
A. N. VERMEULEN
Affiliation:
Parasitology R&D, Intervet International BV, PO Box 31, 5830AA Boxmeer, the Netherlands
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Abstract

An Eimeria acervulina protein fraction was identified which conferred partial protection against an E. acervulina challenge infection. From this fraction a 37 kDa protein was purified and its corresponding cDNA was cloned and shown to encode a lactate dehydrogenase (LDH). Full length cDNAs encoding LDH from two related species, E. tenella and E. maxima, were also cloned. The homology between the primary amino acid sequences of these three Eimeria LDH enzymes was rather low (66–80%), demonstrating an evolutionary divergence. The Plasmodium LDH crystal structure was used to generate a 3D-model structure of E. tenella LDH, which demonstrated that the many variations in the primary amino acid sequences (P. falciparum LDH and E. tenella LDH show only 47% identity) had not resulted in altered 3D-structures. Only a single LDH gene was identified in Eimeria, which was active as a homotetramer. The protein was present at similar levels throughout different parasitic stages (oocysts, sporozoites, schizonts and merozoites), but its corresponding RNA was only observed in the schizont stage, suggesting that its synthesis is restricted to the intracellular stage.

Keywords

EimeriaApicomplexalactate dehydrogenasevaccine

Information

Type
Research Article
Information
Parasitology , Volume 128 , Issue 6 , June 2004 , pp. 603 - 616
Copyright
2004 Cambridge University Press

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