Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction

Bernardo J Foth, Isheng J Tsai, Adam J Reid, Allison J Bancroft, Sarah Nichol, Alan Tracey, Nancy Holroyd, James A Cotton, Eleanor J Stanley, Magdalena Zarowiecki, Jimmy Z Liu, Thomas Huckvale, Philip J Cooper, Richard K Grencis, Matthew Berriman

    Research output: Contribution to journalArticlepeer-review

    120 Citations (Scopus)

    Abstract

    Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here the whole-genome sequences of the human-infective Trichuris trichiura and the mouse laboratory model Trichuris muris. On the basis of whole-transcriptome analyses, we identify many genes that are expressed in a sex- or life stage-specific manner and characterize the transcriptional landscape of a morphological region with unique biological adaptations, namely, bacillary band and stichosome, found only in whipworms and related parasites. Using RNA sequencing data from whipworm-infected mice, we describe the regulated T helper 1 (TH1)-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identified numerous new potential drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection.
    Original languageEnglish
    Pages (from-to)693-700
    Number of pages8
    JournalNature Genetics
    Volume46
    Issue number7
    Early online date15 Jun 2014
    DOIs
    Publication statusPublished - Jul 2014

    Keywords

    • Animals
    • Gene Expression Profiling
    • Genome, Helminth
    • Host-Parasite Interactions
    • Humans
    • Intestines
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Phylogeny
    • Species Specificity
    • Th1 Cells
    • Trichuriasis
    • Trichuris

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