The filarial nematodes Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus are round worms that infect humans and cause the diseases lymphatic filariasis (lymphedema and hydrocele) and onchocerciasis (river blindness). An estimated 200 million people are infected with these worms and, in a proportion of the infected population, cause severe morbidity and even death. Current drugs used to interrupt the transmission of these worms to uninfected persons, while very effective at killing the first stage larvae, present with problems. The drugs require several years of annual administration (5-15 years). Additionally, there is evidence for resistance developing.
All three of these filarial nematodes contain essential, obligate endosymbiotic bacteria of the genus Wolbachia. Using tetracycline or derivatives of tetracycline (doxycycline), Wolbachia can be depleted from worms in infected animal models of filariasis and human patients. Worms that have been depleted of their endosymbionts are no longer to develop. In adult female worms, depletion of Wolbachia results in a permanent block in oogenesis and embryogenesis. Recently, we have shown that depletion of the endobacteria from W. bancrofti and O. volvulus results in death of the adult worms at the site of infection. Because of these spectacular effects, Wolbachia have gained great interest as targets for controlling filarial infections. However, little is known about the endosymbiotic relationship between Wolbachia and their nematode hosts.
My group has three research areas. The first is to understand the symbiosis between Wolbachia and filarial nematodes at the molecular level. One way to research this question is to characterize nematode genes that are differentially regulated during tetracycline treatment to deplete the endobacteria. Using this method, we have successfully identified a phosphate permease that is up-regulated in female and male worms as Wolbachia are depleted. Recently we have extended these results using the B. malayi micro-array chip to identify more genes that may be involved in symbiosis.


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