Project description:We report the presence of Onchocerca ochengi and O. volvulus derived small RNAs in bovine nodule fluids and human serum and plasma, respectively. Further comparisons with other related filarial nematodes like Litomosoides sigmodontis and Dirofilaria immitis reveal common and distictive signatures associated to the Onchocerca species.
Project description:We sequenced total RNA from Dirofilaria immitis in order to generate the first tissue-specific gene expression profile of a filarial nematode and its Wolbachia endosymbiont.
Project description: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 two homologs of transforming growth factor 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 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.
