Genome-wide characterization of folate transporter proteins of eukaryotic pathogens

Abstract

Background: Medically important pathogens are responsible for the death of millions every year. For many of these pathogens, there are limited options for therapy and resistance to commonly used drugs is fast emerging. The availability of genome sequences of many eukaryotic protozoa is providing important data for understanding parasite biology and identifying new drug and vaccine targets. The folate synthesis and salvage pathway are important for eukaryote pathogen survival and organismal biology and may present new targets for drug discovery. Methods: We applied a combination of bioinformatics methods to examine the genomes of pathogens in the EupathDB for genes encoding homologues of proteins that mediate folate salvage in a bid to identify and assign putative functions. We also performed phylogenetic comparisons of identified proteins. . Results: We identified 234 proteins to be involve in folate transport in 63 strains, 28 pathogen species and 12 phyla, 60% of which were identified for the first time. Many of the genomes examined contained genes encoding transporters such as folate-binding protein YgfZ, folate/pteridine transporter, folate/biopterin transporter, reduced folate carrier family protein, folate/methotrexate transporter FT1. The mitochondrion is the predicted location of the majority of the proteins, with 15% possessing signal peptides. Phylogeny computation shows the similarity of the proteins identified. Conclusion: These findings offer new possibilities for potential drug development targeting folate-salvage proteins in eukaryotic pathogens.