Codes for Killers: Knowledge of microbes could lead to cures

Scientists have deciphered the DNA of the parasites responsible for three deadly diseases: African sleeping sickness, Chagas’ disease, and leishmaniasis. This information could open new routes to preventing and treating these conditions, which collectively kill more than 1 million people worldwide each year.

The diseases are caused by related protozoa in a group known as trypanosomatids—single-celled organisms that are transmitted back and forth between at least two hosts, often a blood-eating insect and a person. African sleeping sickness, caused by Trypanosoma brucei, gradually brings on devastating neurological symptoms that affect the sleep cycle. Chagas’ disease, caused by Trypanosoma cruzi, critically damages the heart, stomach, and brain. Leishmaniasis, caused by various species of Leishmania protozoa, can lethally enlarge the spleen and liver.

“These are neglected diseases that afflict deeply impoverished people in the developing world,” says Najib El-Sayed of the Institute for Genomic Research in Rockville, Md. As such, he adds, they have traditionally been unattractive research projects for pharmaceutical companies hoping to turn a profit. No vaccine exists to prevent these conditions, and the drugs that are currently available are considered inadequate because of their toxicity or the parasites’ acquired resistance.

After procuring grants in the late 1990s to study the organisms that cause these conditions, several groups collaborated to sequence the parasites’ genomes. The teams were El-Sayed’s group at the Institute for Genomic Research and groups at the Wellcome Trust Sanger Institute in Hinxton, England, the Seattle Biomedical Research Institute, and the Karolinska Institute in Stockholm.

After examining the sequences of T. brucei, T. cruzi, and Leishmania major, the researchers made several surprising discoveries. For example, says Matthew Berriman of the Wellcome Trust Sanger Institute, the three parasites have a common core of 6,200 genes arranged in a similar order. By creating drugs that interfere with proteins produced by these shared genes, but not proteins produced by people, scientists may be able to treat all three diseases with few or no side effects.

Berriman also notes that the differences between the three parasites’ genomes provide clues to why these organisms are so deadly. For example, the research teams identified more than 800 genes for surface proteins that T. brucei mixes and matches to evade immune system detection. “This gives us more information on why vaccines are going to be difficult to design for this organism,” Berriman says.

The results of the genome studies, published together in the July 15 Science, are important not only for their potential impact on treating these diseases but also for setting a positive example for collaborative research, notes Thomas Brewer of the Bill & Melinda Gates Foundation in Seattle. “These are not only good science, but they’re good in terms of synergism,” he says.

John Kelly, who studies these and related protozoa at the University of London, notes that the next step will be to figure out which parasite proteins make the best targets for drug design. He predicts that the three genome studies will provide “a whole sea of targets that we can look at in detail.”