Filarial nematode

Wolbachia endosymbionts are abundant in arthropods, where they promote a variety of reproductive manipulations, including feminization of genetic males, parthenogenesis and cytoplasmic incompatibility. Wolbachia is also present in filarial nematodes and has recently attracted a great deal of attention. This chapter reviews the studies so far published and discusses potential implications and future research prospects. Since this is a relatively young field, the chapter will also refer to unpublished studies and will include some speculation. The aim is to stimulate further work on the subject. 

The Discovery and Rediscovery of Intracellular Symbiosis in Filarial Nematodes... 

Intracellular symbiosis is extremely widespread in invertebrates. For example, mutualistic symbioses with intracellular bacteria can be found in almost all animal phyla, including sponges, cnidaria, nematodes, anellids, mollusca and arthropoda. Buchner (1965) thoroughly reviews most information published on bacterial symbiosis in animals up to 1964. After this monumental work, various reviews on more specific subjects have been published (e.g. Baumann, 1998, and references therein) including some recent reviews on Wolbachia (O Neill et al., 1997 Werren, 1997). In most of these papers, the term symbiosis is apparently used with a broad meaning the intracellular bacterium is usually referred to as an endosymbiont even in the absence of data on effects on host fitness. Here only key points on intracellular symbiosis and Wolbachia will be summarized, so as to put the information available on symbiosis in filarial nematodes into a broader context. 

Within the body of filarial nematodes, intracellular bacteria have been observed by electron microscopy in the lateral cords of both males and females. Within the cell cytoplasm, the bacteria are in membrane-bound vacuoles. In some cases, the cytoplasm of lateral cord cells is filled by bacteria these bacteria-filled cells resemble in some ways insect bacteriocytes (Baumann et al, 1998). In female worms, bacteria are present also in the oogonia, oocytes, developing embryos and in the cell layer surrounding... 

Exhaustive surveys have not been carried out to determine the prevalence of infection within a single species of filarial nematode. However, infection was found in all eight specimens of D. immitis collected from worldwide locations, indicating that infection prevalence is likely to be close to 100% (Sironi et al., 1995). Sequences of Wolbachia ftsZ genes from... 

Table 2.1. Filarial nematodes infected with intracellular bacteria. The method of detection is shown. Neither electron microscopy nor the immuno-histochemical staining techniques used are to be regarded as Wolbachia specific (see note). Positive identification of intracellular bacteria as Wolbachia is shown only where PCR amplified products of rRNA or ftsZ genes have been sequenced. ...

Immuno-histochemical staining of intracellular bacteria in filarial nematodes has been obtained using antibodies against GroELand catalase (Henkle-Duhrsen etal., 1998 Hoerauf etal., 1999) the specificity of these antibodies is unknown, but it is expected to be low because both GroEL and catalase show high level of amino acid conservation throughout the proteobacteria. nd = not done. 

Fig. 2.1. A tree representing the phylogeny of Wolbachia in arthropods (groups A and B) and filarial nematodes (groups C and D). Group designations correspond to those proposed by Werren etal. (1995) and by Bandi etal. (1998). The names at the terminal nodes are those of the host species. The tree is based on the ftsZgene sequence alignment used by Bandi etal. (1998). The tree was obtained using a distance matrix method (Jukes and Cantor correction neighbour-joining method).

Comparison of host and symbiont phylogenies is a powerful method for assessing the occurrence and frequency of horizontal transmission (Moran and Baumann, 1994). There are limited sequence data available for assessing the phylogeny of filarial nematodes. Comparison of Wolbachia... 

In view of the diversity of reproductive effects induced by arthropod Wolbachia, it would not be surprising if Wolbachia behaves in different ways in different filarial nematodes. The C and D Wolbachia groups are estimated to have diverged approximately 100 million years ago (see earlier). Given this fact, it is quite possible that Wolbachia in different lineages have followed different evolutionary trajectories. 

The effectors of the mammalian host immune attack against filaria include reactive oxygen intermediates. Filarial nematodes express glutathione peroxidase, thioredoxin peroxidase and superoxide dismutase at their surface - enzymes believed to protect the nematode from this attack (Selkirk et al., 1998). A bacterial catalase gene has been identified that most probably derives from the endosymbiont genome (Henkle-Duhrsen et al., 1998) this enzyme may contribute with other enzymes to the protection of both Wolbachia and its nematode host from oxygen radicals. 

This chapter focuses on Wolbachia in filarial nematodes. EM studies have also revealed intracellular bacteria in other nematodes (e.g. Shepperd et al., 1973 Marti et al., 1995) and the bacterial endosymbionts of plant pathogenic nematodes belonging to the genus Xiphinema have recently been identified as belonging to the verrucomicrobia group (Vandekerckhove et al., 2000). However, most nematode bacteria are still to be identified. These may also play important roles in nematode biology. 

Implications for treatment. It has recently been shown that tetracycline inhibits the development of filarial nematodes from L3 to L4 in vitro (Smith and Rajan, 2000, Experimental Parasitology 95, 265-270). However, chloramphenicol, erythromycin and ciprofloxacin failed to inhibit the... 

Bandi, C., Anderson, T.J.C., Genchi, C. and Blaxter, M. (1998) Phylogeny of Wolbachia in filarial nematodes. Proceedings of the Royal Society of London B 265, 2407-2413. 

Hoerauf, A., Nissen-Pahle, K., Schmetz, C., Henkle-Duhrsen, K., Blaxter, M.L., Buttner, D.W., Gallin, M., Al-Qaoud, K.M., Lucius, M. and Fleischer, B. (1999) Tetracycline therapy targets intracellular bacteria in the filarial nematode... 

M. B., Tanya, V.N., Donnely, M.J. and Trees, A.J. (2000) Macrofilaricidal activity of tetracycline against the filarial nematode Onchocerca ochengi elimination of Wolbachia precedes worm death and suggests a dependent relationship. Proceedings of the Royal Society of London B 267, 1063-1069. 

Selkirk, M.E., Smith, V.P., Thomas, G.R. and Gounaris, K. (1998) Resistance of filarial nematode parasites to oxidative stress. International Journal for Parasitology 28, 1315-1332. 

Taylor, M.J., Cross, H.F. and Bilo, K. (2000) Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria. Journal of Experimental Medicine 191, 1429-1436. 

Cookson, E., Blaxter, M. and Selkirk, M. (1992) Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione-peroxidase. Proceedings of the National Academy of Sciences USA 89, 5837-5841. 

Lewis, E., Hunter, S., Tetley, L., Nunes, C., Bazzicalupo, P. and Devaney, E. (1999) cMt-i-like genes are present in the filarial nematodes, Brugia pahangi and Brugia malayi, and, as in other nematodes, code for components of the cuticle. Molecular and Biochemical Parasitology 101, 173-183. 

Selkirk, M.E., Nielsen, L., Kelly, C., Partono, F., Sayers, G. and Maizels, R.M. (1989) Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi. Mokcular and Biochemical Parasitology 32, 229—246. 

Singh, R.N. and Mehta, K. (1994) Purification and characterization of a novel transglutaminase from filarial nematode Brugia malayi. European Journal of Biochemistry 225, 625—634. 

The hatching of the first larval stage of filarial nematodes, the microfilaria (mf), from the eggshell is quite different from the process in other... 

McKerrow, J.H., Huima, T. and Lustigman, S. (1999) Do filarial nematodes have a vascular system Parasitology Today 15, 123. 

Warbrick, E., Barker, G., Rees, H. and Howells, R. (1993) The effect of invertebrate hormones and potential hormone inhibitors on the third larval moult of the filarial nematode, Dirofilaria immitis, in vitro. Parasitology 107, 459-463. 

Wu, Y., Adam, R, Williams, S.A. and Bianco, A.E. (1996) Chitinase genes expressed by infective larvae of the filarial nematodes, Acanthocheihnema viteae and Onchocerca volvulus. Molecular and Biochemical Parasitology 75, 207—219. 

Fig. 15.5. Structures of A/-linked glycans from several different species of parasitic nematodes, illustrating both similarities with mammalian glycans (compare with Figs 15.1 and 15.2) and features unique to nematodes (e.g. tyvelose and PC capping and novel core fucosylation). The filarial nematode glycans are believed to be substituted with charged residues, which are not yet characterized.

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