Researchers reveal genetic secrets of devastating human parasite

Sep 20, 2007

An international team of researchers has revealed the genetic secrets of one of the world’s most debilitating human parasites, Brugia malayi (B. malayi), which the World Health Organization estimates has seriously incapacitated and disfigured more than 40 million people around the globe.

The study, which appears in the September 21 issue of the journal Science, reveals dozens of potential new targets for drugs or vaccines and should provide new opportunities for understanding, treating and preventing elephantiasis, the disfiguring disease caused by the B. malayi parasite. In addition, understanding how this particular parasite has adapted to humans may help organ transplant researchers, according to the authors.

More than 150 million people worldwide are infected with filarial parasites—long, thread-like microscopic worms that can live for years inside the human body and cause severe, debilitating diseases. The female B. malayi worms can live up to eight years in the human body, eventually leading to a ghastly, disfiguring disease known as elephantiasis, which is characterized by excessive buildup of lymphatic fluid in the body and extreme swelling in limbs, trunk or head. People can be affected when bitten by infected insects or spiders.

The longevity of this parasite complicates treatment because existing drugs target the larvae and, thus, do not completely kill the worms. The drugs often must be taken periodically for years, and the worm can cause a massive immune reaction when it dies and releases foreign molecules in the body.

According to first author, Elodie Ghedin, Ph.D., assistant professor of infectious diseases, University of Pittsburgh School of Medicine, having a complete genetic blueprint of the organism will undoubtedly lead to the development of much better therapies. “The genomic information gives us a better understanding of what genes are important for different processes in the parasite’s life cycle. So, it will now be possible to target these genes more specifically and interrupt its life cycle,” explained Dr. Ghedin, who led the sequencing project while at The Institute for Genome Research, which is now part of the J. Craig Venter Institute, a not-for-profit research organization in Bethesda, Md.

Dr. Ghedin led a team of scientists from research institutions around the globe in analyzing the 90 million base pair genome of B. malayi. From the sequence analysis, they predicted approximately 14,500 to 17,800 protein coding regions, or genes, in the B. malayi genome, which was in agreement with previous estimates. Comparative analysis of the B. malayi genome with that of another nematode, Caenorhabditis elegans, revealed that more than 20 percent of the predicted proteins in B. malayi are specific to the parasite.

Based on this finding, Dr. Ghedin and her colleagues suggested that these B. malayi-specific genes—almost 2,000 in all— constitute an “interesting list” of initial candidates for functional studies of the gene products. In addition, from the genome sequence, Dr. Ghedin and her co-investigators identified several metabolic pathways containing dozens of gene products that they believe are likely to be helpful for the discovery of more targeted and effective drug therapies. These include pathways involved in molting, nuclear receptor responses, collagen processing, neuronal signaling, protein phosphorylation (i.e., protein kinases) and host and endosymbiont metabolism.

“Insights into the gene activation pathways of B. malayi will undoubtedly speed the pace of discovery of new treatments. And any new interventions to reduce the burden of disfiguring elephantiasis around the world will indeed be welcome,” said Donald Burke, M.D., dean of the University of Pittsburgh Graduate School of Public Health.

In addition, when the researchers compared the sequences of predicted gene products (proteins) of B. malayi to that of interleukins, chemokines and other immune signaling molecules from humans, they identified a number of candidates they believe are responsible for allowing the nematode to evade immune detection. According to the investigators, these proteins may be immune modulators that promote the survival of the parasite or allow its development.

Understanding how this particular parasite has adapted to humans may yield medical benefits far beyond treating elephantiasis, says collaborator Alan L. Scott, Ph.D., of the Bloomberg School of Public Health at Johns Hopkins University. “Parasitic worms are a lot like foreign tissue that has been transplanted into the human body. But unlike baboon hearts or pig kidneys, which the immune system quickly recognizes as foreign and rejects, worms can survive for years in the body. Discovering how they do so may someday benefit transplant surgery,” explained Dr. Scott.

Source: University of Pittsburgh

Explore further: Free the seed: OSSI nurtures growing plants without patent barriers

add to favorites email to friend print save as pdf

Related Stories

Scientists identify most proteins made by parasitic worm

May 23, 2011

A team led by Thomas B. Nutman, M.D., of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has completed a large-scale analysis of most of the proteins produced ...

Insight into the evolution of parasitism

Sep 22, 2008

Scientists at the Max Planck Institute for Developmental Biology, together with American colleagues, have decoded the genome of the Pristionchus pacificus nematode, thereby gaining insight into the evolution ...

Recommended for you

Plants with dormant seeds give rise to more species

Apr 18, 2014

Seeds that sprout as soon as they're planted may be good news for a garden. But wild plants need to be more careful. In the wild, a plant whose seeds sprouted at the first warm spell or rainy day would risk disaster. More ...

Researchers successfully clone adult human stem cells

Apr 18, 2014

( —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

User comments : 0

More news stories

Biologists help solve fungi mysteries

( —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Researchers successfully clone adult human stem cells

( —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.