Approximately one in four people globally, and countless domesticated animals, are infected by parasitic helminths. Although infection by parasitic helminths has been largely eradicated in developed countries, parasitic helminths still exist as a public health problem in many third world countries. Parasitic helminthic infections in marginalized populations have been recognized to impede socioeconomic development, exacerbate poverty, and make infected individuals more susceptible to infection by malaria and HIV/AIDS. Although antihelminthic drugs currently exist, many of these drugs are nonspecific, and may harm the host. This, concurrent with the increased cases of antihelminthic drug resistance, has made the search or new antihelminthic drug targets vital. Rhodoquinone (RQ) has been identified to be an excellent candidate for selective anti-helminthic drug therapy because it is used by parasitic helminthes, but not mammalian hosts. This is due to differences in the metabolic pathways between the host and parasite: mammalian hosts use ubiquinone (Q) as the main electron carrier in aerobic respiration; inside the anaerobic environment of the host, parasitic helminthes use RQ as the main electron carrier as part of the fumarate reductase pathway. To understand the biosynthesis of RQ in parasitic helminthes, Caenorhabditis elegans will be used as the model organism. Genes potentially involved with RQ production have been identified using bioinformatics, and are as follows: asns-1, asns-2, coq-3, coq-4, coq-5, coq-7, and nkat-1. The candidate genes were knocked down via RNAi feeding experiments. RNAi clones were transformed into Escherichia coli, which were then fed to C. elegans in liquid cultures. The lipids from each transgenic line of C. elegans were extracted, and the RQ content was analyzed via liquid chromatography – mass spectroscopy. Changes in RQ content in a transgenic population would indicate the gene’s role in RQ production, and provide a gene target for future studies.

Identification of genes involved in RQ9 biosynthesis in C. elegans using RNAi knockdowns

249th National Meeting (2015)

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