Protein expression of short-chain dehydrogenases/reductases and their inducibility by flubendazole in Haemonchus contortus

Short-chain dehydrogenases/reductases (SDRs) are a vast family of enzymes involved in both internal metabolism and the breakdown of foreign substances in parasites like the gastrointestinal nematode Haemonchus contortus. Researchers have discovered that SDRs might help the parasite resist the effects of flubendazole, a benzimidazole-type anthelmintic. This study aimed to analyze the constant presence of SDR genes and how they respond to flubendazole in both ordinary and resistant strains of H. contortus.

Through quantitative PCR, scientists assessed the expression of 23 sdr genes in the parasites. To further evaluate the proteins produced, they used targeted proteomic assays to measure 15 SDR proteins. They found that the expression patterns of these proteins varied between adult males and females, with differences even greater between drug-resistant and drug-susceptible nematodes.

In adult nematodes, they observed distinct sex-dependent variations in both the genes and proteins. The resistance-related changes were less significant and primarily seen in males. Specifically, four SDR genes – SDR9, SDR12, SDR15, and SDR20 – were found to have higher protein quantities in the resistant strain of nematodes. When exposed to flubendazole, juvenile nematodes showed only slight increases in SDR gene expression, while adult nematodes experienced noticeable sex- and strain-specific reactions. The most marked changes were found in the resistant male nematodes.

Interestingly, the strongest effects on SDR expression were seen in resistant males, and significant changes in protein levels were only observed in adult nematodes from the drug-susceptible strain. The SDR9 and SDR20 genes stood out, as they exhibited both resistance-associated expression patterns and responsiveness to flubendazole exposure.

In summary, this targeted proteomic study of SDRs in H. contortus identified several SDR isozymes that are either constantly overexpressed in resistant nematodes or get activated by flubendazole. This suggests that these SDR enzymes might play a crucial role in helping the parasite adapt to anthelmintic treatments.