Identification of clinically approved small molecules that inhibit growth and affect transcript levels of developmentally regulated genes in the African trypanosome

摘要

African trypanosomes are unicellular parasites that infect humans and animals, causing a fatal disease known as sleeping sickness in humans and nagana in cattle. These diseases impose a severe economic burden for people living in Sub-Saharan Africa, where parasites are transmitted to humans and animals through the bite of the tsetse fly. Parasites living outside cells in humans and animals are attacked by the antibodies of the host immune system, but they can evade this attack by varying the proteins on their cell surface. In contrast, because flies do not have an antibody-mediated immune response, parasites living in flies do not vary the proteins on their cell surface. In this study, we performed a small molecule screen to identify compounds that either inhibit parasite growth or that affect transcript levels of genes associated with the transition to the insect stage. Parasites that are more similar to the insect-stage would be expected to be vulnerable to the mammalian immune system. We found 3 compounds that increased RNA levels for a gene that codes for an insect-stage surface protein. We also identified 154 compounds that inhibit parasite growth, and we hope these compounds might have potential as novel trypanosomiasis therapeutics.