title: TIMPs of parasitic helminths - a large-scale analysis of high-throughput sequence datasets.
abstract: BACKGROUND
  Tissue inhibitors of metalloproteases (TIMPs) are a multifunctional family of proteins that orchestrate extracellular matrix turnover, tissue remodelling and other cellular processes. In parasitic helminths, such as hookworms, TIMPs have been proposed to play key roles in the host-parasite interplay, including invasion of and establishment in the vertebrate animal hosts. Currently, knowledge of helminth TIMPs is limited to a small number of studies on canine hookworms, whereas no information is available on the occurrence of TIMPs in other parasitic helminths causing neglected diseases.
  
  
  METHODS
  In the present study, we conducted a large-scale investigation of TIMP proteins of a range of neglected human parasites including the hookworm Necator americanus, the roundworm Ascaris suum, the liver flukes Clonorchis sinensis and Opisthorchis viverrini, as well as the schistosome blood flukes. This entailed mining available transcriptomic and/or genomic sequence datasets for the presence of homologues of known TIMPs, predicting secondary structures of defined protein sequences, systematic phylogenetic analyses and assessment of differential expression of genes encoding putative TIMPs in the developmental stages of A. suum, N. americanus and Schistosoma haematobium which infect the mammalian hosts.
  
  
  RESULTS
  A total of 15 protein sequences with high homology to known eukaryotic TIMPs were predicted from the complement of sequence data available for parasitic helminths and subjected to in-depth bioinformatic analyses.
  
  
  CONCLUSIONS
  Supported by the availability of gene manipulation technologies such as RNA interference and/or transgenesis, this work provides a basis for future functional explorations of helminth TIMPs and, in particular, of their role/s in fundamental biological pathways linked to long-term establishment in the vertebrate hosts, with a view towards the development of novel approaches for the control of neglected helminthiases.
authors.affiliation: Center for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, Queensland, Australia. cinzia.cantacessi@jcu.edu.au
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cantacessi
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.forename: Darren
authors.initials: D
authors.lastname: Pickering
authors.forename: Severine
authors.initials: S
authors.lastname: Navarro
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D049751:Genome, Helminth; D015801:Helminth Proteins / Q000235:genetics*; D006376:Helminths / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D059467:Transcriptome
chemical_list: D015801:Helminth Proteins; D019714:Tissue Inhibitor of Metalloproteinases