The diversity of ABC transporter genes across the Phylum Nematoda.

Abstract

It is estimated that one billion people globally are infected by parasitic nematodes, with children, pregnant women, and the elderly particularly susceptible to morbidity from infection. Control methods are limited to de-worming, which is hampered by rapid re-infection and the inevitable development of anthelmintic resistance. One family of proteins that has been implicated in nematode anthelmintic resistance are the ATP binding cassette (ABC) transporters. ABC transporters are characterized by a highly conserved ATP-binding domain and variable transmembrane regions. A growing number of studies have associated ABC transporters in anthelmintic resistance through a protective mechanism of drug efflux. Genetic deletion of P glycoprotein type ABC transporters in Caenorhabditis elegans demonstrated increased sensitivity to anthelmintics, while in the livestock parasite, Haemonchus contortus, anthelmintic use has been shown to increase the expression of ATP transporter genes. These studies as well as others, provide evidence for a potential role of ABC transporters in drug resistance in nematodes. In order to understand more about the family of ABC transporters, we used hidden Markov models to predict ABC transporter proteins from 108 species across the phylum Nematoda and use these data to analyze patterns of diversification and loss in diverse nematode species. We also examined temporal patterns of expression for the ABC transporter family within the filarial nematode Brugia malayi and identify cases of differential expression across diverse life-cycle stages. Taken together, our data provide a comprehensive overview of ABC transporters in diverse nematode species and identify examples of gene loss and diversification in nematodes based on lifestyle and taxonomy.