Scientists decode genome of deadly parasitic worm

Najib El-Sayed, associate professor in the University of Maryland's College of Chemical and Life Sciences, led the transatlantic research team, along with Matthew Berriman of the UK's Wellcome Trust Sanger Institute. Their work is published in the July 16, 2009 edition of Nature and featured on the journal's cover.

Schistosomiasis is one of several neglected tropical diseases prevalent across much of Africa, Asia, and South America and affects mainly poor populations living in areas where water is unsafe, sanitation inadequate, and basic health care unavailable. It impacts adults and children's capacity to work and learn, and often leads to death. Knowing this parasite's genome sequence, scientists will now be able to develop much-needed new treatments for schistosomiasis, for which a vaccine does not yet exist. The drug commonly used to treat this parasitic infection does not prevent re-infection, and there are growing reports of drug resistance and treatment failures.

“We have used state of the art genetic and computational approaches to decipher the genome of this pathogen and to facilitate drug discovery,” said El-Sayed, senior author of the paper. “Many promising leads for drug development targets have emerged.”

The paper reports the analysis of approximately 12,000 genes encoded in the nuclear DNA of Schistosoma mansoni, the flatworm that causes schistosomiasis. This comprehensive genome sequence enabled researchers to map out metabolic networks that are essential to survival of the parasite, thereby revealing potential areas of vulnerability. Through bioinformatics and chemogenomic screens, the study also explores cost effective ways to develop new therapies, such as the possibility that existing pharmaceutical drugs might be used to target schistosomiasis.

“We deliberately looked for similarities between us and the parasite so that we may be able to exploit the activities of existing drugs, marketed for different purposes” said Berriman (joint senior author) of the study.

The researchers compared S. mansoni genes with known 'druggable' protein targets of the human host and human-infective pathogens in use by pharmaceuticals on the market; matches indicate potential for existing drugs to be repurposed as anti-schistosomal drugs.

“The accomplishment of sequencing the S. mansoni genome is the critical first step in developing the drugs and vaccines we urgently need to effectively combat schistosomiasis,” said Peter Hotez, Distinguished Research Professor and Chair of the Department of Microbiology, Immunology, and Tropical Medicine at George Washington University and President of the Sabin Vaccine Institute. “It is one of the most important neglected tropical diseases, with evidence suggesting that it may be as important as better known conditions such as malaria or HIV, because of the number of people it affects with chronic, debilitating infections.”

For a sidebar with S. mansoni image: The S. mansoni parasite has a complex life cycle, perpetuated by poor water conditions. The parasite's eggs hatch in water, enter into snail hosts, then travel to human hosts through contaminated water sources, such as bathing and swimming areas. The mature fluke worm grows in the human blood vessel system, depositing eggs around the bladder or intestines, which triggers the formation of excess connective tissue in those regions. The parasite's eggs are passed to the liver or exit through the urine or feces, continuing the cycle of infection.

This work was supported primarily by grants from the National Institutes of Health (NIAID) and the Wellcome Trust. For further information, please contact Najib El-Sayed by e-mail at elsayed@umd.edu or by telephone at +1 (301) 405-2999.

Najib El-Sayed is an Associate Professor of Cell Biology and Molecular Genetics with a joint appointment in the Center for Bioinformatics and Computational Biology at the University of Maryland Institute for Advanced Computer Studies (UMIACS). He is also affiliated with the Maryland Pathogen Research Institute (MPRI). The El-Sayed research group is currently focused on decoding and comparing the genomes of a variety of human pathogens (with the goal of better understanding mechanisms of virulence) and unveiling interactions between pathogen and host proteins. Another ongoing project uses metagenomic approaches to investigate the gut microbial population in children with autism spectrum disease.

July 16 Issue of Nature: http://www.nature.com/nature/index.html