TIMPs of parasitic helminths – a large-scale analysis of high-throughput sequence datasets

Particle and Fibre Toxicology

Alex Loukas¹  Makedonka Mitreva²  Severine Navarro¹  Darren Pickering¹  Andreas Hofmann³  Cinzia Cantacessi¹ 

[1] Center for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, Queensland, Australia;The Genome Institute, Washington University School of Medicine, St. Louis, MO, USA;Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Queensland, Australia

关键词: Functional inferences;    Protein structure;    Bioinformatics;    Transcriptomics;    Excretory/secretory products;    Parasitic helminths;    Tissue inhibitors of metalloproteases;   

Others  :  1227026
DOI  :  10.1186/1756-3305-6-156

 received in 2013-04-05, accepted in 2013-05-28,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Cantacessi et al.; licensee BioMed Central Ltd.

【 图 表 】

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