The role of Wolbachia in the biology and pathogenesis of filariasis

Filarial nematodes are important helminth parasites of the tropics and a leading cause of global disability. A unique feature of these nematodes is their dependency on a symbiotic intracellular bacterium, Wolbachia, for normal development and fertility. This apparent mutualism between nematode and bacteria has been exploited as a novel target for chemotherapy using antibiotics. The bacteria are also a major cause of inflammatory immune activation. The release of the bacteria or bacterial-encoded molecules from the nematode is associated with activation of immune responses associated with adverse reactions to treatment and the pathogenesis of onchocerciasis (“river blindness”). Antibody responses to Wolbachia are associated with the presentation of chronic inflammatory disease in lymphatic filariasis, suggesting that activation of acquired immunity by Wolbachia may trigger the progression toward chronic filarial disease. The completion of the genome of the Wolbachia endosymbiont from Brugia malayi (w Bm) offers suggestions as to which metabolites might be potentially provided by w Bm to the nematode and which may be required by the endosymbiont and provided by the nematode. It may be possible to identify drugs already available that might inhibit key biochemical pathways in Wolbachia, leading to sterility or killing of the adult worms. Comparative analysis of other Wolbachia genomes will help to pinpoint common biochemical pathways for drug targeting.