TY - JOUR
T1 - TIMPs of parasitic helminths - A large-scale analysis of high-throughput sequence datasets
AU - Cantacessi, Cinzia
AU - Hofmann, Andreas
AU - Pickering, Darren
AU - Navarro, Severine
AU - Mitreva, Makedonka
AU - Loukas, Alex
N1 - Funding Information:
This work was supported by a program grant from the National Health and Medical Research Council of Australia (NHMRC). AL and CC are supported by a NHMRC principal research fellowship and early-career research fellowship, respectively. The authors would like to thank Dr Alex Strongin (Sanford-Burnham Medical Research Institute, La Jolla, CA, USA) for helpful discussions on TIMP/MMP interactions.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Bioinformatics
KW - Excretory/secretory products
KW - Functional inferences
KW - Parasitic helminths
KW - Protein structure
KW - Tissue inhibitors of metalloproteases
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=84878234265&partnerID=8YFLogxK
U2 - 10.1186/1756-3305-6-156
DO - 10.1186/1756-3305-6-156
M3 - Article
C2 - 23721526
AN - SCOPUS:84878234265
SN - 1756-3305
VL - 6
JO - Parasites and Vectors
JF - Parasites and Vectors
IS - 1
M1 - 156
ER -