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

Stuart D. Armstrong, Dong Xia, Germanus S. Bah, Ritesh Krishna, Henrietta F. Ngangyung, E. James La Course, Henry J. McSorley, Jonas A. Kengne-Ouafo, Patrick W. Chounna-Ndongmo, Samuel Wanji, Peter A. Enyong, David W. Taylor, Mark L. Blaxter, Jonathan M. Wastling, Vincent N. Tanya, Benjamin L. Makepeace (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
104 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2554-2575
Number of pages22
JournalMolecular and Cellular Proteomics
Volume15
Issue number8
Early online date1 Aug 2016
DOIs
Publication statusPublished - Aug 2016

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Stage-specific proteomes from onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle'. Together they form a unique fingerprint.

Cite this