Three deadly parasite genomes sequenced

An international group of researchers working in more than 20 laboratories around the globe have determined genetic blueprints for the parasites that cause three deadly insect-borne diseases: African sleeping sickness, leishmaniasis and Chagas disease. The research, funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is published in this week’s issue of Science. Knowing the full genetic make-up of the three parasites–Trypanosoma brucei, Trypanosoma cruzi and Leishmania major–could lead to better ways to treat or prevent the diseases they cause.

“Although relatively unfamiliar in the United States, the collective misery caused by these diseases throughout the world is considerable. Having these genomes in hand will give us many new targets for drug and vaccine development,” says NIAID Director Anthony S. Fauci, M.D.

All three diseases are spread by insects. T. brucei, which causes sleeping sickness, is spread by the tsetse fly and is found in sub-Saharan Africa. The World Health Organization estimates there may be as many as 500,000 cases of sleeping sickness each year. If left untreated, sleeping sickness is fatal. Various forms of leishmaniasis are spread by the sandfly and are endemic in 88 countries on five continents. Visceral leishmaniasis, also known as kala azar, is the most severe form of the disease and causes high fever, a swollen spleen and severe weight loss before killing its victims. Cutaneous leishmaniasis, also known as “Baghdad boil,” produces numerous skin ulcers that can leave sufferers permanently scarred. Some 1,000 American service members have been diagnosed with cutaneous leishmaniasis according to testimony by Walter Reed Army Institute of Research’s Alan Magill, M.D., at an Institute of Medicine meeting in May 2005. T. cruzi causes Chagas disease and is spread through the infected feces of an insect sometimes called the “kissing bug” for its habit of biting near a person’s mouth. Found throughout Central and South America, Chagas disease is particularly prevalent among the poor and claims 50,000 lives each year.

NIAID supported the sequencing projects through grants to Kenneth Stuart, Ph.D., and Peter Myler, Ph.D., of Seattle Biomedical Research Institute (SBRI); to Najib El-Sayed, Ph.D., of The Institute for Genome Research (TIGR), Rockville, MD; and to Bjorn Andersson, Ph.D, of the Karolinska Institute in Stockholm, Sweden.

“One of the biggest surprises to come out of the genome sequencing projects is that these parasites–despite major differences in how they are spread and how they cause disease–nevertheless have a core of 6,200 genes in common,” says Martin John Rogers, Ph.D., of NIAID’s Parasitology and International Programs Branch. At a genetic level, the similarities among these parasites outweigh their differences. The shared genes give scientists a vastly expanded array of targets for development of new drugs that conceivably could work against all three parasites, explains Dr. Rogers. Conversely, he adds, analyzing the relatively smaller ways in which the organisms diverge genetically could help researchers design vaccines, drugs and improved diagnostics targeted to each of the three parasites.

In addition to the publication of the three genomes, this week’s issue of Science also includes a paper by NIAID grantee Rick Tarleton, Ph.D., of the University of Georgia, Athens, detailing T. cruzi’s proteome–the set of expressed proteins encoded by its genome. This is a significant achievement, notes Dr. Rogers, because T. cruzi, like many parasites, has multiple forms in its lifecycle and produces differing suites of proteins at each stage. The proteomic analysis revealed the presence of numerous stage-specific proteins, providing clues about how the parasite exploits its insect and mammalian hosts. This, in turn, suggests ways to battle the parasite with drugs specific to each life stage, says Dr. Rogers. At present, there are few therapies for Chagas disease, the condition caused by T. cruzi parasites, and the available drugs are ineffective and have significant adverse side effects. Taken together, Dr. Rogers says, the wealth of information contained in the sequenced genomes opens new avenues to tackle these often forgotten diseases.