A Potential Role for the Interaction of <i>Wolbachia</i> Surface Proteins with the <i>Brugia malayi</i> Glycolytic Enzymes and Cytoskeleton in Maintenance of Endosymbiosis

<div><p>The human filarial parasite <i>Brugia malayi</i> harbors an endosymbiotic bacterium of the genus <i>Wolbachia</i>. The <i>Wolbachia</i> represent an attractive target for the control of filarial induced disease as elimination of the bacteria affects molting, reproduction and survival of the worms. The molecular basis for the symbiotic relationship between <i>Wolbachia</i> and their filarial hosts has yet to be elucidated. To identify proteins involved in this process, we focused on the <i>Wolbachia</i> surface proteins (WSPs), which are known to be involved in bacteria-host interactions in other bacterial systems. Two WSP-like proteins (<i>w</i>Bm0152 and <i>w</i>Bm0432) were localized to various host tissues of the <i>B. malayi</i> female adult worms and are present in the excretory/secretory products of the worms. We provide evidence that both of these proteins bind specifically to <i>B. malayi</i> crude protein extracts and to individual filarial proteins to create functional complexes. The <i>w</i>Bm0432 interacts with several key enzymes involved in the host glycolytic pathway, including aldolase and enolase. The <i>w</i>Bm0152 interacts with the host cytoskeletal proteins actin and tubulin. We also show these interactions <i>in vitro</i> and have verified that <i>w</i>Bm0432 and <i>B. malayi</i> aldolase, as well as <i>w</i>Bm0152 and <i>B. malayi</i> actin, co-localize to the vacuole surrounding <i>Wolbachia</i>. We propose that both WSP protein complexes interact with each other via the aldolase-actin link and/or via the possible interaction between the host's enolase and the cytoskeleton, and play a role in <i>Wolbachia</i> distribution during worm growth and embryogenesis.</p>