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Stage-specific proteomes from Onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle.

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Armstrong, Stuart D, Xia, Dong, Bah, Germanus S, Krishna, Ritesh, Ngangyung, Henrietta F, LaCourse, James ORCID: https://orcid.org/0000-0001-9261-7136, McSorley, Henry J, Kengne-Ouafo, Jonas A, Chounna-Ndongmo, Patrick W, Wanji, Samuel, Enyong, Peter A, Taylor, David W, Blaxter, Mark L, Wastling, Jonathan M, Tanya, Vincent N and Makepeace, Benjamin L (2016) 'Stage-specific proteomes from Onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle.'. Molecular & cellular proteomics : MCP, Vol 15, Issue 8, pp. 2554-2575.

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Abstract

In spite of 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The aetiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilise the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4,260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin-domain family, which was originally identified from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome across the lifecycle highlights its profound complexity and emphasises the extremely close relationship between O. ochengi and O. volvulus The insights provided here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WW Ophthalmology > Diseases. Color Perception > WW 160 Eye infections. Hypersensitivity diseases (General or not elsewhere classified)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1074/mcp.M115.055640
Depositing User: Jessica Jones
Date Deposited: 31 May 2016 10:24
Last Modified: 06 Feb 2018 13:12
URI: http://archive.lstmed.ac.uk/id/eprint/5904

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