Helminths are a class of parasitic worms that are the cause of debilitating infections of 1 in 4 people globally. They are especially prevalent, and thus a larger problem in developing countries. Medications that are being used to treat helminth infections do not specifically target the parasites, and cause undesirable side-effects to mammalian hosts. The need for new drug therapies for parasitic helminth infections is crucial, as resistance to existing medications has been observed in animal infections, and is predicted to soon be a major issue in human infection cases. The Shepherd Lab is investigating the biosynthesis of rhodoquinone (RQ), which is produced in parasitic helminths, but not in mammals (the hosts of parasitic infections). RQ is a required electron carrier in the fumarate reductase pathway in parasites that is utilized during anaerobic growth while inside hosts. A novel drug therapy would target and inhibit the synthesis of RQ, thus specifically harming helminthes, but not their mammalian hosts. In order to inhibit RQ biosynthesis, the genes that are involved in RQ production must first be identified. To identify a potential gene target involved in RQ biosynthesis, gene candidate Rru_A3004 was selected in Rhodospirillum rubrum using RNAseq and bioinformatics. This gene was knocked out via homologous recombination to create a deletion mutant, and RQ levels in lipid extracts from the knockout were determined using LC-MS and compared with wild-type R. rubrum RQ levels. If gene Rru_A3004 is involved in RQ biosynthesis, significantly lower levels of RQ in the deletion mutant are expected when compared to wild-type, making Rru_A3004 a viable gene target for future potential drug therapies.

Effects of deletion of the Rru_A3004 gene on rhodoquinone biosynthesis in Rhodospirillum rubrum

249th National Meeting (2015)

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