|Scientists Sequence Genome of Intestinal Parasite
that Afflicts Hikers and Kids in Daycare
Giardia lamblia is a strange-looking parasite that swims in the
gut, spreads through stool, persists in contaminated water, and
is responsible for more than 20,000 reported infections a year
in the United States. Now it has finally spilled its genetic secrets.
In the September 28, 2007, issue of the journal Science, an international
team of researchers led by scientists at the Marine Biological
Laboratory (MBL) in Woods Hole, MA, and funded by the National
Institute of Allergy and Infectious Diseases (NIAID), one of the
National Institutes of Health (NIH), describes the complete genetic
sequence of the parasite.
The bane of hikers drinking from mountain streams and of small
children in daycare, G. lamblia is the most common intestinal parasite
identified by public health laboratories in the United States,
according to a 2005 report by the Centers for Disease Control and
Prevention. Analysis of its genome has already shed light on the
organism's evolution and revealed opportunities for future research.
"Existing drugs can effectively treat people with Giardia infections,
but as with many pathogens, the concern is that the parasite will
develop resistance to these medications," says NIAID Director Anthony
S. Fauci, M.D. "The Giardia lamblia genome shows us that the parasite
has a large complement of unusual proteins that are potential targets
for new drugs or vaccines."
Giardia spends one phase of its lifecycle in the environment and
the other in the gut of an infected human or wild animal. To maintain
this dual existence, the parasite has two radically different microscopic
In water, Giardia exists as a hardy, highly infectious cyst, which
can survive for months, even in fresh water devoid of all nutrients.
In the gut, Giardia exists in a swimming and feeding form known
as a trophozoite.
The awakening of the dormant cyst happens quickly after someone
swallows contaminated water or food. After the cysts encounter
the warm acidic juices in the stomach, they change into trophozoites.
Within about two hours, these trophozoites will be swimming in
Unlike many other parasites, trophozoites do not invade tissues
or cells. Instead they simply attach to cells, drink in nutrients
and multiply. The parasite evades the immune system and persists
in the intestine by shifting the proteins it displays on its surfaces.
Giardia performs this molecular chicanery so well that half of
all people who are infected are unaware that they even harbor the
parasite. Symptoms for the unfortunate other half include nausea,
diarrhea, bloating and abdominal cramping. Because trophozoites
cling to intestinal cells that absorb fats and nutrients, such
infections can lead to severe complications such as poor nutrient
absorption and weight loss.
Existing drugs can effectively treat people with Giardia infections,
the disease known as giardiasis, but most infections resolve on
their own. When trophozoites detach from the intestinal wall, they
may swim and reattach to new intestinal cells, or they may pass
down the digestive tract and into the bowels, transform back into
cysts and be passed through the stools.
The completed genome is a publicly available resource that should
help advance research on new ways to treat or prevent Giardia infections
because it provides scientists with a comprehensive dossier of
the parasite's genes — often an important first step in designing
potential new drugs and vaccines. These "targets" include genes
the parasite uses to make proteins involved in crucial stages of
infection, evading the immune system, shifting between its two
forms and feeding.
Besides providing new drug and vaccine targets, the parasite's
genome also has provided clues to its evolution. An evolutionary
curiosity, Giardia is a member of the protist kingdom, which with
the animal, plant and fungi kingdoms make up the domain of eukaryotes.
All eukaryotic organisms share certain key characteristics — chief
among them, a defined nucleus containing genetic material.
Eukaryotic organisms are so diverse that they include everything
from amoebae to humans. But even within such a wide range, Giardia
is unusual. In its trophozoite form, it has two nuclei instead
of the more usual one. When it becomes a cyst, it multiplies its
genetic material into four identical nuclei. But despite having
these multiple copies of its nuclei, Giardia is really a genetic
minimalist. It has fewer and simpler genetic components than most
Why? According to one theory, Giardia is simple because it has
lost complexity: evolutionary pressure favors parasites that shed
genes coding for functions they can borrow from their infected
hosts. An alternative theory holds that the parasite may have always
been simple because it diverged from other eukaryotic organisms
more than a billion years ago, long before the complex modern eukaryotes
emerged. Hilary Morrison, Ph.D., and Mitchell Sogin, Ph.D., of
MBL, who led the study, say their findings support this latter
theory. Careful analysis of the genome reveals that Giardia's molecular
machinery — even for the most basic processes usually shared
by other eukaryotes—is simple by comparison. This suggests that
it has always been so. Its parasitic niche has allowed it to maintain
its simple genetic makeup for billions of years — long before
it started showing up at daycare centers.
Along with Drs. Morrison, Sogin and their MBL colleagues, collaborators
on the project included researchers from the University of California,
San Diego; the University of Texas at El Paso; University of Arizona
College of Medicine; University of Illinois at Urbana–Champaign;
Uppsala University in Sweden; the University of Zürich; Boston
University Goldman School of Dental Medicine; the Karolinska Institute
in Sweden; the Salk Institute for Biological Studies; and the University
Since 1998, NIAID has supported the sequencing of many genomes
of pathogenic microorganisms, including those considered emerging
and re-emerging, as well as potential agents of bioterrorism. For
more information about NIAID's large-scale sequencing efforts,
Giardia lamblia sequence data is freely available to the scientific
community and the public through GenBank, an Internet-accessible
database of genetic sequences maintained by the National Center
for Biotechnology Information (NCBI) at NIH's National Library
of Medicine. To access GenBank, see http://www.ncbi.nlm.nih.gov/Genbank/GenbankSearch.html.
To view a graphic illustrating the life cycle of Giardia lamblia,
NIAID is a component of the National Institutes of Health. 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 basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies.
News releases, fact sheets and other NIAID-related materials are
available on the NIAID website at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 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 it investigates the causes, treatments, and cures for both
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its programs, visit www.nih.gov.
Reference: H Morrison et al. Genomic minimalism
in the early diverging, intestinal parasite, Giardia lamblia. Science 10.1126/science.1143837