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Tag: nematodes

Ghosts of symbionts past: The hidden history of the dynamic association between filarial nematodes and their Wolbachia endosymbionts

graphical abstract

Many, but not all, parasitic filarial nematodes (Onchocercidae) carry intracellular, maternally-transmitted, alphaproteobacterial Wolbachia symbionts. The association between filarial nematodes and Wolbachia is often portrayed as mutualist, where the nematode is reliant on Wolbachia for an essential but unknown service. Wolbachia are targets for anti-filarial chemotherapeutic interventions for human disease. Wolbachia of Onchocercidae derive from four of the major supergroups (C, D, F and J) defined within the genus. We explored the evolutionary history of the filarial nematode-Wolbachia symbiosis in twenty-two nematode species, sixteen of which have current Wolbachia infections, by screening the nematode nuclear genome sequences for nuclear Wolbachia transfers, fragments of the Wolbachia genome that have been inserted into the nuclear genome. We identified Wolbachia insertions in five of the six species that have no current Wolbachia infection, showing they have previously had and have now lost Wolbachia infections. In currently-infected species we found a diversity of origins of the insertions, including many cases where they derived from a different supergroup to the current live infection. Mapping the origins of the insertions onto the filarial nematode phylogeny we derive a complex model of evolution of Wolbachia symbiosis. The history of association between Wolbachia and onchocercid nematodes includes not only cospeciation, as would be expected from a mutualist symbiosis, but also loss (in the five Wolbachia-free species), frequent symbiont replacement, and dual infection. This dynamic pattern is challenging to models that assume host-symbiont mutualism.

Emmelien Vancaester, Guy R Oldrieve, Alex Reid, Georgios Koutsovoulos, Dominik R Laetsch, Benjamin L Makepeace, Vincent Tanya, Sven Poppert, Jürgen Krücken, Adrian Wolstenholme, Mark Blaxter. G3 (Bethesda). 2025 Oct 1:jkaf226. doi: 10.1093/g3journal/jkaf226.

EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor

Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while glutamate-gated chloride channels in the pharynx of the nematode are affected by the avermectins. Here we describe a novel nicotinic acetylcholine receptor on the nematode pharynx that is a potential new drug target. This homomeric receptor is comprised of five non-α EAT-2 subunits and is not sensitive to existing cholinomimetic anthelmintics. We found that EAT-18, a novel auxiliary subunit protein, is essential for functional expression of the receptor. EAT-18 directly interacts with the mature receptor, and different homologs alter the pharmacological properties. Thus we have described not only a novel potential drug target but also a new type of obligate auxiliary protein for nAChRs.

Shivani Choudhary, Samuel K. Buxton, Sreekanth Puttachary, Saurabh Verma, Gunnar R. Mair, Ciaran J. McCoy, Barbara J. Reaves, Adrian J. Wolstenholme, Richard J. Martin, Alan P. Robertson. PLoS Pathog. 2020 Apr 3;16(4):e1008396. doi: 10.1371/journal.ppat.1008396.