Swedish Research Council Formas
2017 - 2020
Genomics in Trichomonads; Lateral Gene Transfer, and Targets for New Drugs.
Trichomonads are difficult-to-treat, parasitic eukaryotes infecting animals. Strains resistant to current drugs are being increasingly reported and highlights that trichomonads undergo rapid genetic change to evade antibiotics. The need for new drugs is therefore urgent. Evidence for prokaryote-to-eukaryote lateral gene transfer (LGT) has been revealed in a number of organisms, and it is clear that LGT contribute to the evolution of many eukaryotes. In Trichomonas vaginalis alone we have previously described 149 LGTs. LGTs provide attractive candidates as therapeutic leads – as genes acquired from bacteria by the parasite can be expected to be very different or absent from the genome of the vertebrate host. To evaluate new targets for drugs to treat trichomonads infections we will focus on LGTs in five different species of trichomonads. We will use Next Generation sequencing to collect genome data of trichomonads. We aim to address questions about the evolutionary timeline of LGTs, the fate of recently transferred genes and functions of gene products. This will be accomplished by bioinformatics analyses such as nucleotide and amino acid statistics and phylogeny. Reverse genetics will be used to evaluate predicted functions on enzyme level using specific assays. We will use data mining to nominate inhibitors to hamper enzymatic activities detected. Successful inhibition shown in vitro will be tested also on live cultures to evaluate the effect of inhibitors on trichomonads.