Massively Parallel Sequencing and Analysis of the Necatoramericanus Transcriptome

Cantacessi, Cinzia and Mitreva, Makedonka and Jex, Aaron R. and Young, Neil D. and Campbell, Bronwyn E. and Hall, Ross S. and Doyle, Maria A. and Rabelo, Elida M. and Ranganathan, Shoba and Sternberg, Paul W. and Loukas, Alex and Gasser, Robin B. (2010) Massively Parallel Sequencing and Analysis of the Necatoramericanus Transcriptome. Transcriptome of Adult Necator americanus , 4 (5).

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Background: The blood-feeding hookworm Necator americanus infects hundreds of millions of people worldwide. In order to elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of the adult stage of Necator americanus was explored using next-generation sequencing and bioinformatic analyses. Methodology/PrincipalFindings:A total of 19,997 contigs were assembled from the sequence data; 6,771 of these contigs
had known orthologues in the free-living nematode Caenorhabditis elegans, and most of them encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that the C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative
phosphorylation (63%) and/or proteases (60%); most of these molecules were predicted to be involved in more than one biological pathway. Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. For instance, proteinase inhibitors were inferred to be highly represented in the former species, whereas SCP/Tpx-1/Ag5/PR-1/Sc7 proteins ( = SCP/TAPS or Ancylostoma-secreted proteins) were predominant in the latter. In N. americanus, essential molecules were predicted using a combination of
orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have homologues in the human host. These candidate targets were inferred to be linked to mitochondrial (e.g., processing proteins) or amino acid metabolism (e.g., asparagine t-RNA synthetase). Conclusions: This study has provided detailed insights into the transcriptome of the adult stage of N. americanus and examines similarities and differences between this species and A. caninum. Future efforts should focus on comparative
transcriptomic and proteomic investigations of the other predominant human hookworm, A. duodenale, for both fundamental and applied purposes, including the prevalidation of anti-hookworm drug targets.

Item Type: Article
Subjects: Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Marija Kalejska
Date Deposited: 30 Nov 2012 10:55
Last Modified: 27 Oct 2014 13:30

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