Sexually Transmitted Diseases
Human urogenital trichomoniasis, caused by T. vaginalis is the most prevalent non-viral, sexually transmitted disease with a worldwide estimate in females of 180 million new cases per year, including 3 million in the U.S.A. The disease results in erosion of the vaginal mucosa, the formation of hemorrhagic spots and the production of a foul smelling discharge containing large amounts of putrescine. In addition, trichomoniasis patients have an increased risk of cervical cancer, possibly due to increased epithelial cell proliferation as a result of the putrescine eliminated by the parasite. Although predominantly a female disease, a similar number of U.S. males are also infected and act as asymptomatic carriers of the disease. A recent study suggests that the occurrence of T. vaginalis infections is more common amongst men than is generally appreciated, and further, they demonstrate increased concentrations of HIV-1 in the semen of these men, posing an increased risk of male to female transmission of HIV.
Dr. Yarlett’s group has demonstrated that T. vaginalis, unlike the majority of eukaryotic cells, lacks de novo synthesis of spermine, and is therefore auxotrophic for the higher polyamines. The parasite has an active back-conversion pathway that transforms spermine to spermidine. In addition analogues that inhibit this pathway arrest parasite growth and development. We are also exploring a group of nahthaquinones that are reduced by the parasites low-redox proteins producing toxic products within the parasite.
Student projects include: biochemical assays directed at exploring the metabolism of polyamines by this parasite; Polyamine transport studies directed at characterizing the parasite polyamine transporter; Molecular biology of parasite enzymes; and In-vitro and in-vivo testing of novel antimicrobial agents.