A bioinformatic approach for detecting genetic mutations leading to multidrug resistance in Fasciola hepatica

Abstract

This master thesis deals with a bioinformatic approach for detecting genetic mutations leading to multidrug resistance in the trematode Fasciola hepatica. Enhanced anthelmintic drug efflux by ABC transporters has been assumed to be involved in developing resistance. Therefore, cDNA contigs of ABC transporters of drug sensitive versus resistant individuals were analyzed to identify functional significant mutations. The basic local alignment tool (BLAST) was used to compare the Fasciola hepatica contigs with a database consisting of genetic material of Homo sapiens, Drosophila melanogaster and Caenorhabditis elegans. Therefore, the liver fluke contigs could be characterized and uniquely classified to the single ABC transporter subfamilies. In addition, sequence alignments were conducted by the use of Geneious to organize, visualize and compare the classified contigs. Several point mutations could be detected probably leading to functional changes of the transporters. Furthermore, biological motifs were identified and found to be highly degenerate. These results may provide new insights into the adaption mechanisms the parasites have developed to survive drug exposure.