The Genetic Code Of Parasitic Worm That Causes Elephantiasis Revealed

Science Daily — More than 150 million people worldwide are infected with filarial parasites -- long, thread-like worms that can live for years inside the human body and cause severe, debilitating diseases such as elephantiasis.

Mosquitoes spread the larvae of these parasitic nematodes from human to human, placing at risk more than a billion people who live in places in Africa, Asia and Latin America where filarial parasites thrive.

Now, a team of researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health (NIH), has revealed the genetic secrets of one of these parasites.

In the September 21, 2007 issue of Science, the researchers report solving the complete genome of Brugia malayi, one of the worms that causes the often debilitating disease elephantiasis.

The World Health Organization (WHO) estimates that more than 40 million people around the world are seriously incapacitated and disfigured by elephantiasis. The WHO also estimates that about half a million people around the world have lost their vision due to onchocerciasis, or river blindness, which is caused by another type of filarial parasite.

"Filarial diseases are treatable, but the current treatments were discovered decades ago," says NIAID Director Anthony S. Fauci, M.D. "There is an urgent need for new discoveries in this area because of the limitations of the current drugs, including toxicities and the development of resistance." The B. malayi genome reveals dozens of potential new targets for drugs or vaccines and should provide new opportunities for understanding, treating and preventing elephantiasis and similar diseases.

"Having a complete genetic blueprint gives us a better understanding of what genes are important for different processes so you can target them more specifically," says Elodie Ghedin, Ph.D., who led the sequencing project while at the Institute for Genomic Research, now part of the J. Craig Venter Institute, a not-for-profit research organization based in Rockville, Maryland. Dr. Ghedin is now a professor at the University of Pittsburgh School of Medicine.
When a mosquito bites someone infected with B. malayi, it ingests microscopic worms that develop into infectious larvae. These larvae are then deposited onto the skin of the next person bitten. Once the parasites penetrate the skin, they wend their way to the body's lymphatic system--a network of fine vessels and organs that drains fluid from the body's tissues and plays a key role in coordinating the immune response by concentrating immune cells in the lymph nodes.

Male and female worms cluster, intertwining in the draining vessels just below the lymph nodes, and mate. A fertile female may produce 1,000 or more larvae a day and grow to be three or four inches long.

This filarial union can cause severe disease. Because they most often position themselves in front of vessels draining liquid from the lymph nodes, the worms can effectively obstruct the drainage. This causes the surrounding tissues to fill with fluid and swell to elephantine proportions.

As the disease progresses, tissues in the swelling arms, legs or scrotum can die or become infected, turning black and oozing puss. To make matters worse, the fluid accumulation can lead to permanent disfigurement over time as the swollen limbs become solid masses with connective tissue, blood vessels and nerve endings. Reducing the bulbous tissue may require major surgery.

Female B. malayi worms can live up to eight years in the human body. This longevity complicates elephantiasis treatment because existing drugs for treating the disease target the larvae only and do not completely kill the adult worms. The drugs often must be taken for years, and the worms can cause massive immune reactions when they die, releasing foreign molecules in the body.

The worm's longevity is curious because it lives for years in the shadow of the lymph node, where immune cells meant to clear the body of infections congregate. One way the worm survives is by releasing chemicals that dampen the human immune response. B. malayi is so good at this that most people who are infected have no symptoms: The worms can live in their bodies for years without their even knowing it.

Understanding how this particular parasite has adapted to humans may yield medical benefits far beyond those places where elephantiasis is common, according to collaborator Alan L. Scott, Ph.D., of the Bloomberg School of Public Health at Johns Hopkins University. Worms can be viewed as foreign tissue transplanted into the human body. But unlike baboon hearts or pig kidneys, which the immune system quickly rejects, worms can survive for years in the body.

Discovering how they do so may someday benefit transplant surgery, according to Dr. Scott.
Along with NIAID, J. Craig Venter Institute, and Johns Hopkins, collaborators on the project included researchers from the University of Edinburgh; New England Biolabs; the University of California, Davis Genome Center; Smith College; Imperial College, London; the University of Dundee; Divergence, Inc; Washington University; Lyon College; The Australian National University; the University of Toledo; the New York Blood Center; the Hospital for Sick Children in Toronto; the University of Göttingen; and the University of Alabama.

SCIENCE: Geneticists Crack the Species Code

BROOKLIN, Canada, Sep 14 (IPS) - Scientists are enthusiastic about a new DNA barcoding technology that will help keep illegal fish and timber out of global markets, slow the spread of invasive pests, and improve food safety and disease prevention and offer better environmental monitoring.

U.S. government regulatory agencies such as the Food and Drug Administration (FDA) and National Oceanic and Atmospheric Administration are beginning to utilise the three-year-old technology. "It's now a proven technology, everyone wants to use it," said David Schindel, executive secretary of the Consortium for the Barcode of Life, comprised of 160 scientific and regulatory organisations from 50 countries and based at the Smithsonian Institution in Washington. "It's also an incredibly important technology for developing countries to research and protect their biodversity," Schindel told IPS.

DNA barcoding is a fast, low-cost tool to identify plant and animal species developed in 2003 by Paul Herbert of the Biodiversity Institute of Ontario at Canada's University of Guelph. DNA is found in all living things, and is a complex molecule that contains all the genetic instructions for an organism to develop. Not surprisingly, the DNA of a human is different and more complex than that of a worm -- although mouse DNA is similar to human DNA. The genetic differences within the millions of pieces that make up DNA among animal species were very hard to find. Herbert's breakthrough was the discovery of a portion of a gene that is unique to each animal species -- its "DNA barcode".

This week, 350 DNA experts from 46 nations are meeting in Taipei with health officials, government agencies and others to get a better understanding of how to use this new technology to improve consumer protection and food safety, prevent disease, monitor changes in the environment, and more. Barcoding the world's several thousand species of mosquitoes is expected to become a priority since they are responsible for 500 million human malarial infections and a million deaths each year.

Mosquitoes also transmit many other devastating diseases, like West Nile virus and dengue, as well as parasites. "Key to disease management is vector control," said scientist Yvonne-Marie Linton of London's Natural History Museum, and leader of the Mosquito Barcoding Initiative (MBI). Until now, control efforts have been consistently undermined by species misidentification.

DNA barcoding can tremendously assist the world's expert mosquito taxonomists struggling to keep up with new species discoveries, she added. Researchers elsewhere worldwide are focused on barcoding other biting insects -- blood-sucking pests to birds, people and other mammals alike -- causing diseases, stress and allergic reactions. Another priority is fungi. Ecologically important for life on Earth, some 90-99 percent of fungi remain undocumented. Identifying both disease-producing and medically-useful fungi is important.

Previous meetings in Africa have identified other priorities such as barcoding insect pests that affect crops, fish species and insect pollinators, said Schindel. Networks are being established so that a biologist in Cameroon can take a sample, extract the DNA and send it to a lab there or elsewhere in Africa, where the sample's genes can be sequenced. That gene sequence is then compared with others in Genbank, a massive online database containing nearly 300,000 gene sequences. "If there is no match, then it might be a previously unidentified species, but the sequence will reveal related species," Schindel explained.

There is no cost to access these databanks, and the Consortium is committed to keeping the databases free and open to all, he said. Barcoding is also playing an important role in protecting biodiversity, the complex web of plants and animals that keeps ecosystems healthy. It's impossible to protect countries' biodiversity without knowing what's there, Schindel noted. Moorea, an island in French Polynesia, has become a laboratory for a French-U.S. collaboration that is building a barcode library for all terrestrial and marine species.

In South America, scientists and regulators want to use the technology to identify fish species to better monitor fish stocks and quotas and prevent sales of threatened or endangered species. Equally urgent for countries like Brazil is the ability to quickly identify the species of hardwood tree that a piece of lumber is made from. "When a tree has been turned into a pile of lumber it's very hard to know what species it was," Schindel said.

In the United States, the FDA has already barcoded 100 commercial fish species, following several fatal cases of toxic puffer fish sold as monk fish. The National Oceanic and Atmospheric Administration plans to use barcoding to better regulate commercial fish catches and do research on what fish are eating by analysing the contents of their guts. DNA barcoding also allows for fast identification of invasive species, says Scott Miller, an entomologist at the Smithsonian Institution.

"Invasive species can now come from anywhere in the world because of global transport systems," Miller told IPS. Preventing the spread of invasives is best done early before they become widely established, and the key to early action is identification. "That identification is vital in a region like the Galapagos Islands with so many endemic species easily disrupted by invasives," Miller said.

In 10 years' time or less, Galapagos port officials and inspectors will have a wireless DNA barcoder on their belts to identify species on the spot, he hopes. "Barcoding is expanding our knowledge of nature and is simultaneously providing tangible, specific and significant benefits to society," concluded Schindel.

Garlic and Cow Belching: A Global Warming Cure?

Weird But Possibly True: Garlic Nixes Farm Animals’ Methane Gas

Who knew? Besides the vegan-eatin’ PETA folks that is.

Belching farm animals account for 16% of our planet’s methane, a gas even more responsible for global warming than carbon dioxide. As Popular Science reports in October, a new study has found that lacing the diets of cows with garlic can decrease their, uh, emissions, by up to 50%.

Shaun Lowe/iStock

Time to try this out on family and friends, too!

The question is … will the eventual meat be pre-infused with the fragrance and flavor of garlic?

Radiation Absorbing Mineral Found In the Arctic

"A mineral has recently been found that exhibits the astounding property of being able to remove radiation from water-based solutions. 'After coming into contact with the mineral, radioactive water becomes completely safe. Had this mineral been available to physicists after the Chernobyl or Three Mile Island disasters, the consequences might have been very different, as both accidents resulted in contamination from radioactive water.' Also, the article notes that although only grams of the material have been found, tons of it are needed; they are confident they could artificially reproduce it."

Arctic’s microbes being studied for new discoveries

Y. Mallikarjun

— Photo: Special Arrangement

Microbes from the Arctic could serve as workhorses of biotechnology to catalyse reactions at low temperature.

HYDERABAD: After finding 25 bacterial species in the Antarctica, a scientist here has begun studying the microbial diversity in the Arctic region for discovering new genes, bio-molecules and enzymes with potential applications for biotechnology, pharmaceutical and detergent industries.

S. Shivaji, director-grade scientist, Centre for Cellular and Molecular Biology (CCMB), who collected soil, water and sediment samples from the numerous glaciers and the Arctic ocean to prospect the microbial diversity, told The Hindu here on Wednesday that the microbes from the Arctic could serve as workhorses of biotechnology to catalyse reactions at low temperature. He was part of the five-member First Indian Scientific Expedition to Arctic that returned recently after a trip to the North Pole.

He would look into whether the microbes living in the pristine glaciers of the Arctic are similar to those on the icy continent of Antarctica or unique to their environment. He would also study how they thrive in sub-freezing temperatures when organisms living in tropical conditions cannot survive below 8 degrees C.

Genes identified

Many of the of the discovered species in the Antartica were named in honour of that continent, India and the two Indian permanent stations, Dakshin Gangotri and Maitri located there. Using these organisms, he identified genes required for survival of micro-organisms at sub-zero temperatures and enzymes of biotechnological potential.

Describing the expedition’s experience, he said: “The pristine cold environment embraced us with its purity, cleanliness, glaciers and the colourful ocean. It was literally a top-of-the-world feeling. I was so excited that I wanted to work from the very day of arrival and then realised that during this period, the Arctic was one long day without any night since the sun does not set in the Arctic between May and August. I could sample the numerous glaciers dotting the Ny-Alesund, where we set up our camp”

Explaining the uniqueness of sampling the glaciers in North Pole, he said there was no anthropogenic influence there, unlike anywhere else in the world. Another striking feature of the Arctic, unlike Antarctica, was that 6-7 per cent of the land area was covered with vegetation, including a number of beautiful flowers.

These life forms could serve as excellent model systems to unravel the biological basis of adaptation to low temperature and reveal the various strategies adapted by them to survive and reproduce.