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A bacterial genome reveals new targets to combat infectious disease

More than a billion people are at risk for infection with filarial nematodes, parasites that cause elephantiasis, African river blindness, and other debilitating diseases in more than 150 million people worldwide. The nematodes themselves play host to bacteria that live within their cells, but in this case, the relationship is classic mutualism, with each benefiting from the other. Indeed, the Wolbachia bacterium is so crucial to its host nematode that apparently eradicating it with antibiotics severely compromises the nematode's ability to complete its life cycle within its human host. Thus, understanding the details of this relationship may help identify new strategies for controlling diseases caused by filarial nematodes. In a new study published in the freely-available online journal PLoS Biology, Barton Slatko and colleagues present the complete DNA sequence of the Wolbachia pipientis strain within Brugia malayi, a parasitic nematode responsible for lymphatic filariasis.

This Wolbachia genome is small, only about a million base pairs, and many metabolically critical genes have degraded through mutation to the point of uselessness. This phenomenon, called reductive evolution, is typical of long-term symbioses, as the two partners increasingly complement one another's biochemical activities.

Slatko and colleagues enumerate a variety of pathways that have either been degraded or preserved, and highlight patterns in the genome structure through comparisons with other bacteria. For example, Wolbachia can manufacture some essential metabolic coenzymes, which do not appear to be made by its host. Conversely, it cannot synthesize amino acids and a variety of other vitamins and cofactors, and probably depends on the nematode to supply them.

One discovery of possible significance is the presence in the bacterium of the synthetic pathway for heme - the oxygen-carrying iron component of hemoglobin. The nematode may require heme for synthesis of devel opmental hormones, so Wolbachia's heme pathway may be an inviting target for therapy against nematode infection. Since no new antifilarial has been developed in two decades, these results may quickly lead to new therapeutic strategies against these parasites.

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Citation: Foster J, Ganatra M, Kamal I, Ware J, Makarova K, et al. (2005) The Wolbachia genome of Brugia malayi: Endosymbiont evolution within a human pathogenic nematode. PLoS Biol 3(4): e121.


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Source:PLoS Biology


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