, 2005b; Turner et al., 2010) are also either partially dependent upon the bacterial endosymbionts or alternatively may occur through indirect mechanisms associated with Wolbachia infection. These include protection from oxidative stress, contribution to the nematodes’ evasion and subversion of host immunity. The molecular basis of the mutualistic role of Wolbachia remains unresolved. Comparative genomic analysis of B. malayi Wolbachia (wBm), with other Wolbachia ‘strains’ and related rickettsial species together with that of the host nematode, has revealed that although much of the wBm genome appears degenerate, certain key metabolic pathways remain intact. These pathways

include the biosynthesis of haem, nucleotides, riboflavin and FAD, which are absent from the host nematode genome learn more and related bacteria (Foster et al., 2005; Slatko et al., 2010). Cyclopamine order How and when these factors contribute to the mutualistic association is the subject of ongoing research. One puzzle, which has confounded the broad acceptance of Wolbachia

as an obligate mutualist, is the apparent secondary loss of the endosymbiont from some of the more evolutionarily ‘advanced’ species, including the human filaria, Loa loa, the rodent parasite, Acanthocheilonema viteae, and the deer parasite, Onchocerca flexuosa (Taylor et al., 2005a). Support for the secondary loss of the symbiont comes from genomic sequencing, which showed evidence of Wolbachia gene fragments having been integrated into the host nematode genome through lateral gene transfer (LGT), facilitated by the close association between the bacteria and germline cells (McNulty et al., 2010). The process of LGT appears to be common among Wolbachia insect and nematode hosts, with almost an entire Wolbachia genome inserted into the nuclear genome of Drosophila ananassae (Dunning Hotopp et al., 2007). Although evidence for gene transcription has been reported for some of these LGT events, further work is needed to determine whether they represent a

mechanism by which the nematodes have been able to dispense with the endosymbionts by acquiring the key genes required for obligate mutualism, or whether they simply represent a genetic ‘ghost’ from previous IMP dehydrogenase encounters in their evolutionary history. Another area in which Wolbachia has been shown to play an important role is in driving inflammatory disease pathogenesis and inflammatory adverse reactions to antinematode drugs in lymphatic filariasis, onchocerciasis and heartworm disease (Taylor et al., 2005a; Tamarozzi et al., 2011). The release of Wolbachia bacteria and their products from the nematode has been shown to stimulate the innate and adaptive inflammatory immunity through the recognition of lipoproteins via Toll-like receptors TLR-2 and TLR-6 (Turner et al., 2009). This drives the recruitment of inflammatory cells, leading to damage of parasitized tissues, including the cornea and lymphatics (Taylor et al., 2005a; Turner et al., 2009; Tamarozzi et al.