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Wolbachia Genome Project

Sequencing the Brugia malayi endosymbiont

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The Brugia malayi Wolbachia DNA Sequencing Project

In the process of analyzing the Brugia malayi genome as part of the Filarial Genome Project it was observed that the worms contained Wolbachia, obligate intracellular alpha-proteobacteria which are present in all human and many animal filarial parasites. Related organisms are present in up to 70% of arthropod species. In arthropods, the Wolbachia have been shown to cause reproductive abnormalities in their hosts, leading to aberrant sex ratios, reciprocal cross sterility (cytoplasmic incompatablities), parthenogenesis and feminization of genetic males.

Treatment of host animals with the antibiotic tetracycline results in developmental abnormalities of various life cycle stages of the parasites that carry Wolbachia. Effects on embryogenesis are prominent among these phenotypes. These effects correlate with depletion of the bacterial population within the filarial parasites.

Further, there appear to be effects of Wolbachia upon the pathogenesis of filarial disease mediated by the lipopolysaccharide induction of inflammation responses by the host.

Wolbachia have been observed in the majority of parasitic filarial nematodes and these endosymbionts appear to play important roles in the biology of the host. Wolbachia are thus promising targets for development of vaccines against filarial infections. Genomic sequence will hopefully provide information to enable the development of appropriate therapeutics.

Filariasis

Many devastating diseases in tropical areas of the world are the result of infection with parasites. A recent World Health Organization (WHO) report on the leading causes of death world-wide shows that 1/3 are due to infectious and parasitic diseases. In many tropical and subtropical areas, the prevalence of parasitic infections is on the rise due to rapid and unplanned growth of cities, which creates additional breeding sites for the mosquitoes that transmit the parasites responsible for malaria and filariasis. Effective control of these diseases requires repeated administration of potent drugs and continuous efforts to reduce vector insect populations.

Filariasis is caused by several different species of parasitic nematodes that are transmitted to humans by insect vectors. Collectively, the various species of filarial parasites are estimated to infect approximately 150 million people worldwide, and over 1 billion people live in areas where filariasis is common. While filarial infection is rarely life-threatening, it causes chronic suffering, social stigma and disability. The degree of disability resulting from infection greatly hinders the ability to work and the economic impact of this disease is considerable. Brugia malayi is a filarial nematode with widespread distribution in South and South East Asia. It is transmitted via the bite of blood-feeding mosquitoes. The parasite resides in the lymphatic system and is a cause of lymphatic filariasis. In the later stages of infection, the disease is characterized by a disfiguring condition known as elephantiasis. Onchocerca volvulus is the causative agent of River Blindness and the second leading cause of blindness worldwide. This filarial parasite is transmitted by blackflies that breed in fast flowing rivers. Over 20 million people are infected world-wide although approximately 99% of cases are found in Africa.

Currently available anti-parasitic drugs have their limitations and there is a need to focus on the discovery of new drugs to ameliorate the conditions associated with the various diseases and to control the parasites responsible.

For more than 20 years, NEB has supported basic research in molecular parasitology. It is hoped that this research may contribute towards the development of technologies that can control filarial parasites and therefore improve the quality of life in areas where filarial infections are endemic. The parasitology group at NEB has been working, in collaboration with a number of scientists from various universities and institutions, to discover new potential targets for antiparasite chemotherapy.

     
   
   
   
Elephantiasis of the lower leg, one of the visble symptoms of Bancroftian filariasis (upper image) and ocular lesions in an onchocerciasis (river blindness) victim lead to blindness (lower image). Images provided by the World Health Organization (WHO)/ United Nations Development Program / World Bank/ WHO Special Program for Research and Training in Tropical Diseases.
   
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