|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
“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, Maryland; 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
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.
In addition to NIAID, The Wellcome Trust, London, supported
the T. brucei and L. major genome sequencing projects.
NIAID is a component of the National Institutes of
Health, an agency of the U.S. Department of Health and
Human Services. NIAID supports basic and applied research
to prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research
on transplantation and immune-related illnesses, including
autoimmune disorders, asthma and allergies.
The National Institutes of Health (NIH) — The
Nation's Medical Research Agency — is comprised
of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services.
It is the primary Federal agency for conducting and
supporting basic, clinical, and translational medical
research, and investigates the causes, treatments,
and cures for both common and rare diseases. For more
information about NIH and its programs, visit www.nih.gov.