MOLECULAR MECHANISMS OF FILARIAL ENDOSYMBIOSIS (New York Blood Center) (NIH)

Nematodes cause the most common parasitic infections of humans, and the tissue-dwelling filarial worms produce the most severe pathology associated with these infections. Current control programs, however, which are universally based upon the mass distribution of a small arsenal of drugs are exceptionally vulnerable to failure in the event resistance develops. What is lacking is a method to kill or permanently sterilize the adult female parasites, making it critically important to support additional research leading to the discovery of novel drug targets. Most filarial worm species carry a Wolbachia endosymbiont that can be eliminated by treating with antibiotics, which affects molting, reproduction, and survival of the worms, indicating that the Wolbachia are crucial for the development of the parasite. Our goal for this project is to define the mechanisms that determine the interdependencies between the parasitic nematode Brugia malayi and its bacterial endosymbiont.