Alterations in cytochrome-c oxidase expression between praziquantel-resistant and susceptible strains of Schistosoma mansoni

C. PEREIRA a1, P. G. FALLON a2p1, J. CORNETTE a1, A. CAPRON a1, M. J. DOENHOFF a2 and R. J. PIERCE a1c1
a1 INSERM U167 ‘Relations hôte-parasite et stratégies vaccinales’, Institut Pasteur de Lille, 59019–Lille, France
a2 School of Biological Sciences, University of Wales, Bangor, Gwynedd, UK


The genetic differences between praziquantel-resistant (R) and susceptible (S) strains of Schistosoma mansoni (Fallon & Doenhoff, 1994) were explored using RAPD and by cloning differentially expressed mRNAs by subtractive PCR. No differences between the 2 strains were detectable by RAPD using 41 different primers indicating that no major genomic rearrangements were present. Subtractive PCR generated a number of fragments, 1 of which was shown to correspond to an over-expressed mRNA in the R strain and to encode a fragment of the subunit 1 of cytochrome-c oxidase (SCOX1). In the absence of a complete sequence for this gene, we used EST sequences to compile a consensus sequence for the 904 bp at the 3′ end that enabled us to choose primers for semi-quantitative RT–PCR. This technique showed that SCOX1 was indeed over-expressed about 5 to 10-fold in the R strain whereas the genes encoding the 28 kDa glutathione S-transferase, glutathione peroxidase, NADH dehydrogenase subunit 5 and the ATP-binding cassette family protein SMDR2 were not. In contrast, cytochrome-c oxidase enzyme activity was 4-fold lower in the R strain than in the S strain.

(Received November 20 1997)
(Revised February 5 1998)
(Accepted February 5 1998)

Key Words: Schistosoma mansoni; praziquantel; resistance; EST; cytochrome-c oxidase.

c1 Corresponding author: INSERM U 167, Institut Pasteur de Lille, 59019 – Lille, France. Tel: +33 3 20877783. Fax: +33 3 20877888. E-mail: Raymond.
p1 Present address: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK.