TY - JOUR TI - Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets AU - Curran, David M AU - Grote, Alexandra AU - Nursimulu, Nirvana AU - Geber, Adam AU - Voronin, Dennis AU - Jones, Drew R AU - Ghedin, Elodie AU - Parkinson, John A2 - Harris, Nicola L A2 - Soldati-Favre, Dominique A2 - Harris, Nicola L A2 - Lok, James B VL - 9 PY - 2020 DA - 2020/08/11 SP - e51850 C1 - eLife 2020;9:e51850 DO - 10.7554/eLife.51850 UR - https://doi.org/10.7554/eLife.51850 AB - The filarial nematode Brugia malayi represents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteria Wolbachia—present in many filariae—which is vital to the worm. Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but have only been applied to multicellular eukaryotic organisms more recently. Here, we present iDC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 102 reactions essential to the survival of B. malayi. We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds. KW - brugia malayi KW - metabolic reconstruction KW - flux balance analysis KW - wolbachia KW - metabolomics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -