 |
|
Parasite genome sequences offer hope for new drugs and vaccines, Science studies say
July 15, 2005Scientists have sequenced and compared the genomes of three of the parasites responsible for sleeping sickness, Chagas disease and leishmaniasis, three devastating diseases of the developing world.
These parasites collectively cause disease and death in millions of humans each year, and the new genome sequences provide critical information for drug and vaccine developers, according to new research appearing in the 15 July 2005 issue of the journal Science, published by AAAS, the nonprofit science society.
In addition to offering drug and vaccine leads, the research provides a detailed roadmap of the biology and evolution of these unicellular organisms, or "protozoa," from the family Trypanosomatidae, which parasitize humans and other mammals, birds, reptiles, fish, insects and plants. Insects transmit these disease-causing parasites to humans living in tropical and subtropical regions of the world.
Researchers identified about 6,200 core genes that are present in all three parasites in a similar order within each genome. Some of the proteins encoded in these genes could serve as targets for drugs that would be effective against all three parasites, a worthy goal given the fact that there are currently no vaccines for these diseases, and only a few drugs, most of which are inadequate due to resistance, toxicity or expense.
The sequencing initiative also identified genes specific to each parasite and this information could be useful for parasite-specific drug and vaccine development efforts.
"Thanks to these studies, scientists are now much closer than they were five years ago to developing effective drugs against these terrible diseases," said Science author Najib M. El-Sayed, Assistant Investigator from The Institute for Genomic Research in Rockville, Md.
"These are neglected diseases. The average person in the developed world has not heard of them, but they are absolutely devastating across the developing world," said Science author Matthew Berriman, Senior Computer Biologist from Wellcome Trust Sanger Institute in Hinxton, United Kingdom.
While the three pathogens share many general characteristics, each is transmitted by a different insect, displays unique life cycle features, infects different tissues, evades immune systems in unique ways, and causes different diseases in the humans and the other organisms they infect. All three diseases can lead to severe sickness or death if patients do not receive early treatment.
The 15 July, 2005 issue of Science includes a trio of research articles, each primarily focused one of the parasites, a comparative research article, two related research reports, a "Viewpoint" article and an editorial.
"The original goal of the three genome projects, which were initiated independently, was to decode the genetic blueprint and gain insights into the biology of each of the three parasites. The comparative study is a valuable outgrowth of those projects which has yielded important results," said El-Sayed.
Trypanosoma brucei causes sleeping sickness, also known as Human African trypanosomiasis, and is spread to humans by the notorious tsetse fly. The disease's greatest impact is in Sub-Saharan Africa. Fevers, headaches, joint pains and itching characterize the first phase of the disease. When the parasites cross the blood-brain barrier and enter the central nervous system, they disturb the sleep cycle and other neurological processes.
Trypanosoma cruzi causes Chagas disease. Blood-sucking triatomine bugs, with many different common names including "assassin bugs," live in the cracks and crevices of poor-quality houses in Central and South America and transmit the parasites to humans. People infected with T. cruzi often suffer cardiac, gastrointestinal or neurological damage after decades of persistent infection without disease symptoms.
Leishmania species cause a spectrum of human diseases in Central and South America, southern Europe, Asia, the Middle East and Africa and are transmitted by tiny sand flies. The researchers sequenced the genome of Leishmania major, one of the Leishmania parasites responsible for a skin disease causing sores that often leave disfiguring scars. L. major serves as a model for other Leishmania species, including those causing the internal or "visceral" disease resulting in fever, weight loss and an enlarged spleen and liver and sometimes death.
Now that the genes of these parasites are mapped out, it's much easier to identify genes that are critical for parasite survival. Genes encoding proteins that are involved in critical biological processes often serve as drug targets, said Science author Peter Myler, Research Associate Professor, University of Washington and Scientist, Seattle Biomedical Research Institute, in Seattle, Wash.
The researchers found many genes coding for enzymes not known in humans. For example, the genome project turned up dozens of core genes shared by the three parasites that were probably acquired from bacteria through a process of "horizontal gene transfer." Drugs that hit these acquired enzymes could be fruitful drug targets because they are less likely to affect the host.
Another drug development approach is to focus on proteins that are unique to individual parasites. Many of these species-specific genes are located at the ends of the chromosomes and may encode proteins the parasite needs to survive or cause disease in humans or other host animals. Genes involved in parasite-specific adaptations are unlikely to be shared by their human hosts, making them even more attractive as drug targets.
"Because of their distinct evolution, trypanosomes present a plethora of potential drug targets, and potential drugs are almost certainly languishing in the chemical libraries of pharmaceutical companies," writes George Cross from Rockefeller University in New York, NY. in this week's Science editorial.
Comparing the three genomes also highlights differences in metabolic capabilities of the parasites that reflect the diversity within their lifestyles and correlate with differences in their hosts and vectors. T. brucei has the least overall metabolic capability and L. major has the greatest. The sand flies' ability to feed on nectar may allow L. major to have a more complex sugar metabolism.
In the hopes of developing a T. cruzi vaccine, Science author Rick Tarleton, Research Professor from the University of Georgia in Athens, Ga. and colleagues pieced together which proteins are present within the parasites while they are infecting humans.
"We identified proteins that would make good T. cruzi vaccine candidates and deserve further testing," explained Tarleton.
Lots of unexpected information fell out of this "proteome" analysis, especially related to how T. cruzi obtains energy. Some of these new insights are applicable to drug and vaccine design and others are, at this point, just interesting biology, said Tarleton.
The sequencing of the L. major genome marks an important step toward understanding the genetic differences that make other Leishmania species more dangerous - information critical for efforts to develop a vaccine effective against a broad range of Leishmania species, according to Myler.
Developing vaccines for T. brucei appears less promising because these parasites are so good at escaping the immune system. The new research provides a better look at the vast arsenal of dormant genes thought to help T. brucei in their role as escape artists.
In a paper in the same issue of Science, David Pérez-Morga and colleagues report the mechanism by which a protein found in the serum of humans called "apoL-I" kills African trypanosomes, the parasite responsible for sleeping sickness.
In a "Viewpoint" article, Carlos Morel and colleagues highlight the growing ability of some developing countries to undertake health innovation with their own energies and resources. For example, the majority of the short strands of DNA used to identify the genes of all three parasites were sequenced at institutions in Africa and South America.
American Association for the Advancement of Scienc
Researchers identified about 6,200 core genes that are present in all three parasites in a similar order within each genome. Some of the proteins encoded in these genes could serve as targets for drugs that would be effective against all three parasites, a worthy goal given the fact that there are currently no vaccines for these diseases, and only a few drugs, most of which are inadequate due to resistance, toxicity or expense.
The sequencing initiative also identified genes specific to each parasite and this information could be useful for parasite-specific drug and vaccine development efforts.
"Thanks to these studies, scientists are now much closer than they were five years ago to developing effective drugs against these terrible diseases," said Science author Najib M. El-Sayed, Assistant Investigator from The Institute for Genomic Research in Rockville, Md.
"These are neglected diseases. The average person in the developed world has not heard of them, but they are absolutely devastating across the developing world," said Science author Matthew Berriman, Senior Computer Biologist from Wellcome Trust Sanger Institute in Hinxton, United Kingdom.
While the three pathogens share many general characteristics, each is transmitted by a different insect, displays unique life cycle features, infects different tissues, evades immune systems in unique ways, and causes different diseases in the humans and the other organisms they infect. All three diseases can lead to severe sickness or death if patients do not receive early treatment.
The 15 July, 2005 issue of Science includes a trio of research articles, each primarily focused one of the parasites, a comparative research article, two related research reports, a "Viewpoint" article and an editorial.
"The original goal of the three genome projects, which were initiated independently, was to decode the genetic blueprint and gain insights into the biology of each of the three parasites. The comparative study is a valuable outgrowth of those projects which has yielded important results," said El-Sayed.
Trypanosoma brucei causes sleeping sickness, also known as Human African trypanosomiasis, and is spread to humans by the notorious tsetse fly. The disease's greatest impact is in Sub-Saharan Africa. Fevers, headaches, joint pains and itching characterize the first phase of the disease. When the parasites cross the blood-brain barrier and enter the central nervous system, they disturb the sleep cycle and other neurological processes.
Trypanosoma cruzi causes Chagas disease. Blood-sucking triatomine bugs, with many different common names including "assassin bugs," live in the cracks and crevices of poor-quality houses in Central and South America and transmit the parasites to humans. People infected with T. cruzi often suffer cardiac, gastrointestinal or neurological damage after decades of persistent infection without disease symptoms.
Leishmania species cause a spectrum of human diseases in Central and South America, southern Europe, Asia, the Middle East and Africa and are transmitted by tiny sand flies. The researchers sequenced the genome of Leishmania major, one of the Leishmania parasites responsible for a skin disease causing sores that often leave disfiguring scars. L. major serves as a model for other Leishmania species, including those causing the internal or "visceral" disease resulting in fever, weight loss and an enlarged spleen and liver and sometimes death.
Now that the genes of these parasites are mapped out, it's much easier to identify genes that are critical for parasite survival. Genes encoding proteins that are involved in critical biological processes often serve as drug targets, said Science author Peter Myler, Research Associate Professor, University of Washington and Scientist, Seattle Biomedical Research Institute, in Seattle, Wash.
The researchers found many genes coding for enzymes not known in humans. For example, the genome project turned up dozens of core genes shared by the three parasites that were probably acquired from bacteria through a process of "horizontal gene transfer." Drugs that hit these acquired enzymes could be fruitful drug targets because they are less likely to affect the host.
Another drug development approach is to focus on proteins that are unique to individual parasites. Many of these species-specific genes are located at the ends of the chromosomes and may encode proteins the parasite needs to survive or cause disease in humans or other host animals. Genes involved in parasite-specific adaptations are unlikely to be shared by their human hosts, making them even more attractive as drug targets.
"Because of their distinct evolution, trypanosomes present a plethora of potential drug targets, and potential drugs are almost certainly languishing in the chemical libraries of pharmaceutical companies," writes George Cross from Rockefeller University in New York, NY. in this week's Science editorial.
Comparing the three genomes also highlights differences in metabolic capabilities of the parasites that reflect the diversity within their lifestyles and correlate with differences in their hosts and vectors. T. brucei has the least overall metabolic capability and L. major has the greatest. The sand flies' ability to feed on nectar may allow L. major to have a more complex sugar metabolism.
In the hopes of developing a T. cruzi vaccine, Science author Rick Tarleton, Research Professor from the University of Georgia in Athens, Ga. and colleagues pieced together which proteins are present within the parasites while they are infecting humans.
"We identified proteins that would make good T. cruzi vaccine candidates and deserve further testing," explained Tarleton.
Lots of unexpected information fell out of this "proteome" analysis, especially related to how T. cruzi obtains energy. Some of these new insights are applicable to drug and vaccine design and others are, at this point, just interesting biology, said Tarleton.
The sequencing of the L. major genome marks an important step toward understanding the genetic differences that make other Leishmania species more dangerous - information critical for efforts to develop a vaccine effective against a broad range of Leishmania species, according to Myler.
Developing vaccines for T. brucei appears less promising because these parasites are so good at escaping the immune system. The new research provides a better look at the vast arsenal of dormant genes thought to help T. brucei in their role as escape artists.
In a paper in the same issue of Science, David Pérez-Morga and colleagues report the mechanism by which a protein found in the serum of humans called "apoL-I" kills African trypanosomes, the parasite responsible for sleeping sickness.
In a "Viewpoint" article, Carlos Morel and colleagues highlight the growing ability of some developing countries to undertake health innovation with their own energies and resources. For example, the majority of the short strands of DNA used to identify the genes of all three parasites were sequenced at institutions in Africa and South America.
American Association for the Advancement of Scienc
Parasites Current Events and Parasites News RSSVaccine and drug research aimed at ticks and mosquitoes to prevent disease transmission
Most successful vaccines and drugs rely on protecting humans or animals by blocking certain bacteria from growing in their systems. But, a new theory actually hopes to take stopping infectious diseases such as West Nile virus and Malaria to the next level by disabling insects from transmitting these viruses.
The miseries of allergies just may help prevent some cancers, study finds
There may be a silver -- and healthy -- lining to the miserable cloud of allergy symptoms: Sneezing, coughing, tearing and itching just may help prevent cancer -- particularly colon, skin, bladder, mouth, throat, uterus and cervix, lung and gastrointestinal tract cancer, according to a new Cornell study.
Parasites that live inside cells use loophole to thwart immune system
St. Jude Children's Research Hospital scientists have discovered a mechanism by which intracellular pathogens can shut down one of the body's key chemical weapons against them: nitric oxide.
Researchers characterize potential protein targets for malaria vaccine
Researchers from Nijmegen and Leiden have now characterized a large number of parasite proteins that may prove useful in the development of a human malaria vaccine.
Study rules out inbreeding as cause of amphibian deformities
Although research has linked inbreeding with elevated rates of deformity in a wide variety of animals, a new study finds it plays no part in the high incidence of malformation among salamanders.
Making flies sick reveals new role for growth factors in immunity
A Salmonella infection is not a positive experience. However, by infecting the common laboratory fruit fly Drosophila melanogaster with a Salmonella strain known for causing humans intestinal grief, researchers in the School of Life Sciences at Arizona State University have shed light on some key cell regulatory processes - with broad implications for understanding embryonic development, immune function and congenital diseases in humans.
Mapping a clan of mobile selfish genes
Much of human DNA is the genetic equivalent of e-mail spam: short repeated sequences that have no obvious function other than making more of themselves.
New CU-Boulder study shows diversity decreases chances of parasitic disease
A new University of Colorado at Boulder study showing that American toads who pal around with gray tree frogs reduce their chances of parasitic infections known to cause limb malformations has strong implications for the benefits of biodiversity on emerging wildlife diseases.
Opening a can of worms: Serendipitous discovery reveals earthworms more diverse than first thought
Scientists have found that the UK's common or garden earthworms are far more diverse than previously thought, a discovery with important consequences for agriculture.
Scientists decode genome of parasite that causes relapsing malaria
Scientists have deciphered the complete genetic sequence of the parasite Plasmodium vivax, the leading cause of relapsing malaria, and compared it with the genomes of other species of malaria parasites.
More Parasites Current Events and Parasites News Articles
 | Parasite Rex : Inside the Bizarre World of Nature's Most Dangerous Creatures by Carl Zimmer IMAGINE A WORLD WHERE parasites control the minds of their hosts, sending them to their destruction. IMAGINE A WORLD WHERE parasites are masters of chemical warfare and camouflage, able to cloak themselves with their hosts' own molecules. IMAGINE A WORLD WHERE parasites steer the course of evolution, where the majority of species are parasites. WELCOME TO EARTH. For centuries, parasites have... |
 | The Parasite Menace by Skye Weintraub |
 | Parasite Eve by Hideaki Sena When Dr. Nagashima loses his wife in a mysterious car crash, he is overwhelmed with grief but also an eerie sense of purpose; he becomes obsessed wiht reincarnating his dead wife. Her donated kidney is transplanted into a young girl wiht a debilitating disorder, bu the doctor also feels compelled to keep a small sample of her liver in his laboratory. When these cells start mutating rapidly, a... |
 | Understanding Reptile Parasites (Advanced Vivarium Systems) by Roger Klingenberg |
 | The Mind Parasites by Colin Wilson Wilson has blended H.P. Lovecraft's dark vision with his own revolutionary philosophy and unique narrative powers to produce a stunning, high-tension story of vaulting imagination. A professor makes a horrifying discovery while excavating a sinister archeological site. For over 200 years, mind parasites have been lurking in the deepest layers of human consciousness, feeding on human life force... |
 | The Parasite (Posthumanities) by Michel Serres Influential philosopher Michel Serres’s foundational work uses fable to explore how human relations are identical to that of the parasite to the host body. Among Serres’s arguments is that by being pests, minor groups can become major players in public dialogue—creating diversity and complexity vital to human life and thought. Michel Serres is professor in history of science at the... |
| Overcoming Parasites Naturally by Dr. James R. Overman Control parasites naturally with herbs and the Harmonic Quad... | |
 | Parasites Like Us by Adam Johnson Hailed as “remarkable” by the New Yorker, Emporium earned Adam Johnson comparisons to Kurt Vonnegut and T. C. Boyle. Now, in Parasites Like Us, he takes us on an enthralling journey through memory, time, and the cost of mankind’s quest for his own past. Anthropologist Hank Hannah has just illegally exhumed an ancient American burial site and winds up in jail. But the law will soon be the... |
 | Guess What Came to Dinner?: Parasites and Your Health by Ph. D., CNS, Ann Louise Gittleman With more than 60,000 copies sold, a newly revised and updated edition of an authoritative book on parasitic infections-their detection, treatment, and cure.Once relegated to poor third-world countries, instances of parasitic infections are on a dramatic rise in the United States. In this thoroughly revised and updated edition of Guess What Came to Dinner?, health expert Ann Louise Gittleman... |
 | Parasite Eve 2 Official Strategy Guide by Dan Birlew BradyGAMES Parasite Eve II Official Strategy Guide features Every Item and Key Item, Armor & Weapon Lists, Bonus Items Revealed, Bestiary Stats, Comprehensive Walkthrough and Area Maps. ... |
| © 2008 BrightSurf.com |