title: Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle.
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.
authors.affiliation: From the ‡Institute of Infection & Global Health, University of Liverpool, Liverpool L3 5RF, UK;
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Armstrong
authors.affiliation: From the ‡Institute of Infection & Global Health, University of Liverpool, Liverpool L3 5RF, UK;
authors.forename: Dong
authors.initials: D
authors.lastname: Xia
authors.affiliation: §Institut de Recherche Agricole pour le Développement, Regional Centre of Wakwa, BP65 Ngaoundéré, Cameroon;
authors.forename: Germanus S
authors.initials: GS
authors.lastname: Bah
authors.affiliation: ¶Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK;
authors.forename: Ritesh
authors.initials: R
authors.lastname: Krishna
authors.affiliation: §Institut de Recherche Agricole pour le Développement, Regional Centre of Wakwa, BP65 Ngaoundéré, Cameroon;
authors.forename: Henrietta F
authors.initials: HF
authors.lastname: Ngangyung
authors.affiliation: ‖Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK;
authors.forename: E James
authors.initials: EJ
authors.lastname: LaCourse
authors.affiliation: **The Queens Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4JT;
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.affiliation: ‡‡Research Foundation for Tropical Diseases and Environment, PO Box 474 Buea, Cameroon;
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Kengne-Ouafo
authors.affiliation: ‡‡Research Foundation for Tropical Diseases and Environment, PO Box 474 Buea, Cameroon;
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Chounna-Ndongmo
authors.affiliation: ‡‡Research Foundation for Tropical Diseases and Environment, PO Box 474 Buea, Cameroon;
authors.forename: Samuel
authors.initials: S
authors.lastname: Wanji
authors.affiliation: ‡‡Research Foundation for Tropical Diseases and Environment, PO Box 474 Buea, Cameroon; §§Tropical Medicine Research Station, Kumba, Cameroon;
authors.forename: Peter A
authors.initials: PA
authors.lastname: Enyong
authors.affiliation: From the ‡Institute of Infection & Global Health, University of Liverpool, Liverpool L3 5RF, UK; ¶¶Division of Pathway Medicine, University of Edinburgh, Edinburgh EH9 3JT, UK;
authors.forename: David W
authors.initials: DW
authors.lastname: Taylor
authors.affiliation: ‖‖Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK;
authors.forename: Mark L
authors.initials: ML
authors.lastname: Blaxter
authors.affiliation: From the ‡Institute of Infection & Global Health, University of Liverpool, Liverpool L3 5RF, UK; ‡‡‡The National Institute for Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L3 5RF, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wastling
authors.affiliation: §Institut de Recherche Agricole pour le Développement, Regional Centre of Wakwa, BP65 Ngaoundéré, Cameroon;
authors.forename: Vincent N
authors.initials: VN
authors.lastname: Tanya
authors.affiliation: From the ‡Institute of Infection & Global Health, University of Liverpool, Liverpool L3 5RF, UK; blm1@liverpool.ac.uk.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Makepeace
mesh_terms: D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006790:Host-Parasite Interactions; D006801:Humans; D008297:Male; D009854:Onchocerca / Q000378:metabolism / Q000502:physiology*; D009855:Onchocerciasis / Q000469:parasitology* / Q000662:veterinary; D010802:Phylogeny; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins