Pristionchus species are nematodes that associate with specific beetles and represent a poorly understood but highly prevalent type of nematode-insect interaction known as necromeny. The working model for how Pristionchus nematodes maintain specific insect interactions is by intercepting the intra-species communications of their host insects. Given the multitude of nematode associations with insect and mammalian hosts, the beetle-associated Pristionchus pacificus represents a much needed knowledge bridge between the free-living model organism Caenorhabditis elegans and human filarial nematodes such as Brugia malayi and Wucheria bancrofti. This is especially relevant to human health since filarial nematodes also require insect vectors to transmit diseases such as lymphatic filariasis. Knowledge of the molecular physiology of insect pheromone attraction will have a direct impact on our understanding of olfaction in nematodes, which can ultimately translate into improving treatments against parasitic nematodes that afflict an estimated 1.3 billion people worldwide (WHO). Our recent NIH-funded study revealed that a lipid binding protein, OBI-1, mediates host insect pheromone sensing through the cGMP signaling pathway that is found in many sensory cells of animals. OBI-1 belongs to a class of highly conserved but functionally diverse secreted lipid-binding proteins, including lipopolysaccharide-binding proteins (LBPs), bactericidal permeability-increasing proteins (BPIs), and cholesteryl ester transfer proteins in mammals. We hypothesize that the expression of OBI-1 in the glial cells that support chemosensory neurons is required for the nematode's olfactory organ to recognize the beetle pheromone. We speculate that OBI-1 may act as an extracellular receptor chaperone to guide pheromone molecules to membrane-bound receptors, or as a signal terminator to remove the pheromone from membrane bound receptors. Our primary aims are to determine if OBI-1 mediates olfaction through the glial cells and if there is direct interaction between OBI-1 and the pheromone molecule. Our long-term focus is to interrogate how OBI-1 genetically interacts with other factors the cGMP pathway during odor sensing, such as the cGMP-dependent protein kinase (PKG) EGL-4.
Knowledge of the molecular physiology of insect pheromone attraction in nematodes will have a direct impact on our understanding of olfaction in parasitic nematodes that afflict humans and economically important livestocks and crops. Our proposal has the potential to be translated into improving treatments against human filarial nematodes by targeting their means of perceiving their abiotic environment, their insect hosts, and to elucidate the overall diversity of molecular pathways in animal chemosensation.
|Stephens, David E; Chavez, Gabriel; Valdes, Martin et al. (2014) Synthetic and mechanistic aspects of the regioselective base-mediated reaction of perfluoroalkyl- and perfluoroarylsilanes with heterocyclic N-oxides. Org Biomol Chem 12:6190-9|
|Cinkornpumin, Jessica K; Wisidagama, Dona R; Rapoport, Veronika et al. (2014) A host beetle pheromone regulates development and behavior in the nematode Pristionchus pacificus. Elife 3:|