Authors
A J Mbekeani1; V C Kalel1; E Ruiz1; W Stanley1; M Meissner1; W Schliebs1; R Erdmann1; E Pohl1; P Denny1; 1 Durham University, UKDiscussion
The use of natural products (NP) for treating protozoan infections could be dated back to 1631 in Rome, where cinchona tree bark was used to cure malaria. The discovery of new NP, in the treatment of protozoan diseases is absolutely vital for many of these vaccine deficient protozoan infections. The assessment of NP against Cutaneous Leishmaniasis, was explored using a library of NP screened against the mammalian stage of L. Mexicana in in vitro assays. In addition we also explored the use of a NP, Aureobasidin A and its five derivatives against T. gondii Type I and Type II. Investigating a drug target in T. gondii, we focused on the presence of peroxisomes within T. gondii using Pex proteins. The experimental approach taken involved characterization of putative TgPex5 and it’s associated putative protein ligand TgSCP2. TgSCP2 with a C-terminal Peroxisomal Targeting Signal 1 (PTS1) binds TgPex5, whilst the N-terminal of TgPex5 binds TgPex7. Using molecular biology, reverse genetics and protein characterization, we show that pull-down assays, localisation of TgSCP2, and complementation of TgPex5 and TgPex7 in yeast and human expression systems, we are able to compile evidence to prove or refute the presence of peroxisomes within T. gondii.