Identification and stage-specific expression of two putative P-glycoprotein coding genes in Onchocerca volvulus

Area of Science:

• Molecular Biology
• Parasitology
• Drug Resistance Mechanisms

Background:

• Ivermectin (IVM) resistance in Onchocerca volvulus microfilariae and tolerance in adult worms pose challenges for onchocerciasis control.
• P-glycoprotein (P-gp), known for mediating multidrug resistance, is a potential factor in IVM resistance and tolerance in O. volvulus.

Purpose of the Study:

• To identify P-glycoprotein (P-gp) homologues in Onchocerca volvulus.
• To investigate the potential role of these P-gp homologues in ivermectin (IVM) resistance and tolerance.

Main Methods:

• Reverse transcription polymerase chain reaction (RT-PCR) was used to synthesize cDNA from O. volvulus.
• Two full-length cDNAs, ovpgp-1 and ovplp-1, were cloned and sequenced.
• Semi-quantitative RT-PCR analyzed gene expression patterns across different developmental stages.

Main Results:

• Two P-gp homologues were identified: ovpgp-1 (encoding a full-length P-gp) and ovplp-1 (encoding a smaller P-gp-like protein).
• OVPGP-1 exhibits structural similarity to eukaryotic P-gps.
• Expression levels of ovpgp-1 and ovplp-1 were lower in IVM-sensitive larval stages and higher in IVM-tolerant adult worms.

Conclusions:

• The identified P-gp homologues, particularly ovpgp-1, may play a significant role in ivermectin (IVM) resistance and tolerance in Onchocerca volvulus.
• Differential gene expression suggests a correlation between P-gp levels and IVM sensitivity in different developmental stages of the parasite.