Armstrong, SD and Xia, D and Bah, GS and Krishna, R and Ngangyung, HF and LaCourse, EJ and McSorley, HJ and Kengne-Ouafo, JA and Chounna-Ndongmo, PW and Wanji, S and Enyong, PA and Taylor, DW and Blaxter, ML and Wastling, JM and Tanya, VN and Makepeace, BL (2016) Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle. Mol Cell Proteomics, 15 (8). 2554 - 2575. ISSN 1535-9484

[img]
Preview
Text
J Wastling - Stage-specific proteomes from Onchocerca ochengi.pdf - Accepted Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological 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 utilize 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 4260 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 described 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 emphasizes the extremely close relationship between O. ochengi and O. volvulus The insights presented here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers.

Item Type: Article
Additional Information: This research was originally published in Molecular and Cellular Proteomics. Jonathan Wastling. Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle. Molecular and Cellular Proteomes. 2016; Vol 15:2554-2575. © the American Society for Biochemistry and Molecular Biology
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 01 Sep 2016 08:17
Last Modified: 01 Sep 2016 08:17
URI: http://eprints.keele.ac.uk/id/eprint/2145

Actions (login required)

View Item View Item