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Genomics in Trichomonads; Lateral Gene Transfer, and Targets for New Drugs

Published 2017-03-15

Trichomonadsare difficult-to-treat, parasitic eukaryotes infecting animals. Strains resistant to current drugs are being increasingly reportedand highlights that trichomonads undergo rapid genetic change to evadeantibiotics. The needfor new drugs is therefore urgent. Evidence for prokaryote-to-eukaryotelateral gene transfer (LGT) has been revealed in a number of organisms, and itis clear that LGT contribute to the evolution of many eukaryotes. In Trichomonas vaginalis alone we have previouslydescribed 149 LGTs. LGTs provide attractive candidatesas therapeutic leads – as genes acquired from bacteria by the parasite can beexpected to be very different or absent from the genome of the vertebrate host.To evaluate new targetsfor drugs to treat trichomonads infections we will focus on LGTs in fivedifferent species of trichomonads. We will use Next Generation sequencing tocollect genome data of trichomonads. We aim to address questions about theevolutionary timeline of LGTs, the fate of recently transferred genes andfunctions of gene products. This will be accomplished by bioinformaticsanalyses such as nucleotide and amino acid statistics and phylogeny. Reversegenetics will be used to evaluate predicted functions on enzyme level using specificassays. We will use data mining to nominate inhibitors to hamper enzymaticactivities detected. Successful inhibition shown in vitro will be tested also on live cultures to evaluate the effectof inhibitors on trichomonads.