Project description:Haemonchus contortus is a highly pathogenic parasitic nematode of that can infect a large number of wild and domesticated ruminant species and is the most economically important parasite of sheep and goats worldwide. Although originally a tropical parasite, it has been disseminated around the world by livestock movement and can now be found as far north as the arctic circle. Adult worms are blood feeders that reside in the abomasum (stomach) and are approximately 2cm in length when mature. They are dioecious with single females typically producing several thousand eggs per day which pass out of the host in faeces and develop to infective larvae on the pasture. H. contortus is a member of the superfamily trichostrongyloidea (Strongylida) which contains most of the economically important parasitic nematodes of grazing livestock. These parasites cost the global livestock industry billions of dollars per annum in lost production and drug costs. Resistance to all the major anthelmintic classes is now common worldwide often leading to failure of treatment and control. H. contortus is a close relative of the human hookworm species and belongs to the nearest phylogenetic group of parasites to the free-living model nematode Caenorhabditis elegans . This makes it an important model of parasitic nematode biology that is commonly used for experimental studies. The main objective of this project is to recognize genes expressed in the life stages of H. contortus.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Mobile small RNAs are an integral component of the arms race between plants and fungal parasites, and several studies suggest microRNAs could similarly operate between parasitic nematodes and their animal hosts. However, whether and how specific sequences are selected for export by parasites is unknown. Here we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematode Heligmosomodies bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO is highly conserved and abundantly expressed in related parasites, including the human hookworm and proteomic analyses confirm this is the only Argonaute secreted by rodent parasites. In contrast, exWAGO orthologues in species from the free-living genus Caenorhabditis are highly diverged. By sequencing multiple small RNA libraries, we determined that the most abundant small RNAs released from the nematode parasite are not microRNAs but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. We further identify distinct evolutionary properties of the siRNAs resident in free-living or parasitic nematodes versus those exported in EVs by the parasite and show that the latter are specifically associated with exWAGO. Together this work identifies an Argonaute protein as a mediator of RNA export and suggests rhabditomorph nematode parasites may have co-opted a novel nematode-unique pathway to communicate with their hosts.
Project description:Trichuris muris, the mouse whipworm is used as a laboratory model of the human parasite T. trichuira - a gastrointestinal nematode. Three laboratory isolates of T. muris exist: the E, J and S isolates. Previous data has shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates which are expelled. The ability of the S isolate to persist is still unclear. Microarray analysis of gut samples from mice infected with either the E or S isolates of T. muris for 7 days was used to determine early changes in gene expression that may later determine the outcome of infection.
Project description:MS based secretome analyses of Strongyloides venezuelensis, a gastrointestinal parasite of rats that is widely used as a laboratory model and is known to produce both soluble and insoluble (adhesive) secretions during its parasitic stages.
Project description:The excretory-secretory (ES) proteins are the molecules that actively or passively released by parasite at the parasite-host interface to maintain a physiological and immunological relationship with the host. In the present study, we characterised the excretory-secretory products from the short-term in vitro culture (i.e. within 12 h) of Haemonchus contortus (as the most important parasitic nematodes of livestock animals worldwide) using a high throughput tandem mass-spectrometry underpinned by the most recent genomic dataset. Totally, 878 unique ES proteins from three key developmental stages were identified and quantified without intracellular protein contamination (e.g. histone) typically occurred in longer term maintenance cultures. Bioinformatic analyses showed noteworthy protein excretion and secretion alterations during the transition from the free-living to the parasitic phase, especially for ES proteins which are likely involved in nutrient digestion, acquisition and parasite-host interactions, such as proteolytic cascade related peptidases, glycoside hydrolases, C-type lectins, transthyretin-like proteins and SCP/TAPS proteins. Our finding provide an avenue to better explore interactive processes between the host and this highly significant parasitic nematode, to underpin the search for novel drug and vaccine targets.