BioWorld International Correspondent
LONDON - The genomes of three parasites spread to humans by three different types of insect are remarkably similar, scientists say. Astonishingly for parasites that have such different life styles and insect hosts, the three organisms, which cause sleeping sickness, Chagas disease and leishmaniasis, have about 6,000 genes in common.
Matt Berriman, project leader at the Wellcome Trust Sanger Institute in Hinxton, Cambridgeshire, UK, told BioWorld International: "Some of these 6,000 genes will also be found in other organisms, such as humans, mice and yeast, but we believe that about half are unique to these parasites. There are likely to be important drug targets among these genes and their products, but many of them are completely uncharacterized and this is the next challenge."
Any drug developed that targets a gene product shared by the parasites likely would be effective against all three, Berriman added.
Together, the three diseases kill more than 150,000 people each year, and more than half a billion people are at risk of contracting one of them. N'gana, the animal version of sleeping sickness, results in annual cattle losses estimated at $4 billion.
The effort to sequence the genomes of the three species started almost 10 years ago and involved four genome sequencing centers - the Wellcome Trust Sanger Institute; the Institute for Genomic Research in Rockville, Md.; Seattle Biomedical Research Institute; and the Karolinska Institute in Stockholm, Sweden - together with international teams of researchers from more than 40 laboratories in 21 countries.
Papers detailing the findings appeared in the July 15, 2005, issue of Science. Their titles are "The Genome of the African Trypanosome Trypanosoma brucei;" "The Genome of the Kinetoplastid Parasite, Leishmania major;" and "The Genome Sequence of Trypanosoma cruzi, etiologic agent of Chagas Disease."
Sleeping sickness, which is caused by Trypanosoma brucei and spread by the tsetse fly, is found in sub-Saharan Africa. It is fatal unless treated. Existing drugs are dangerous and effective only at certain stages of the disease.
Trypanosoma cruzi, which causes Chagas disease, is carried by blood-sucking "assassin bugs." It kills 50,000 people each year in Central and South America.
Leishmania major is passed on to humans by the bite of the female sandfly. Different types of leishmaniasis are present in 88 countries on five continents.
Berriman said the genome sequencing work has allowed the researchers to build a comprehensive "road map" of all biochemical reactions in the parasites. "At least 40 genes look like bacterial genes - and in the search for drug targets, these are quite exciting because it increases the chances of making selective drugs," Berriman said.
As well as the similarity in individual genes, their organization and order also are very similar.
In other ways, the parasites' genomes are contrasting. T. brucei has 11 chromosomes and about 23 million bases, L. major has 36 chromosomes with 34 million bases, and T. cruzi has 55 million bases on an indeterminate number of chromosomes.
Studying other differences between the genomes will provide researchers with insights into how L. major invades white blood cells, for example, and how T. brucei is able to develop inside the tsetse fly, and how it evades the human immune system by constantly changing the antigens displayed on its outer surface.
Berriman predicts that, in order to exploit the findings, high-throughput screening of compounds will be needed once researchers identify suitable drug targets.
Bernard Pecoul, executive director of drugs for neglected diseases (DNDi), a nonprofit drug development initiative focused on harnessing public and private sector research and investment to develop new medicines and diagnostics, said: "People suffering these diseases are too poor to provide a profitable market for new medicines. The results of this sequencing project confirm that the science exists for neglected diseases.
"What we need now is public investment to turn this knowledge into affordable, useable medicines for patients and to stimulate much-needed research and development in neglected diseases."