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Exploring the genome of the river blindness parasite

A ‘nest’ of developing Onchocerca volvulus, the parasitic worm that causes river blindness. Thomas Unnasch

River blindness is an eye and skin infection caused by a tiny parasitic worm called Onchocerca volvulus. People acquire the disease through the bite of blackflies that live and breed on the banks of fast-flowing rivers and streams, mostly in sub-Saharan Africa. Once inside the human body, the worms reproduce. Their offspring migrate to the skin, where they cause intense itching and rashes, and to the eye, where they may ultimately cause blindness.

To better understand the parasite, 2 research teams investigated the worm’s genome. The research is described in a pair of papers published online on November 21, 2016, in Nature Microbiology. The teams included scientists employed or supported in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Human Genome Research Institute (NHGRI).

One group, led by Dr. Sara Lustigman at the New York Blood Center, gathered O. volvulus parasites along with samples of Wolbachia, the symbiotic bacteria that live within the worms. The researchers sequenced and examined these genomes. They identified genes that code for common proteins and molecular reactions essential to infection. Based on sequence data, 16 of the newly discovered proteins may be promising targets for existing FDA-approved drugs now used to treat other diseases. More research is needed to determine if interfering with any of these proteins would be a useful strategy for treating river blindness.

River blindness is currently treated with a drug called ivermectin. But some parasites have begun showing resistance to this medication. To learn how this resistance evolved, a research team led by Dr. Makedonka Mitreva at Washington University School of Medicine in St. Louis investigated what the worm’s genome looked like prior to large-scale drug treatment efforts.

The scientists sequenced 27 DNA samples from parasites that had been stored since the early 1990s. They compared the genomes of worms collected from Ecuador, Uganda, and both forest and savannah populations from West Africa. These comparisons helped the team identify genetic markers that can be used to track the evolution of different parasite strains around the globe.

“We want to understand the origin of this [drug] resistance,” Mitreva explains. “Are these parasites evolving to survive the treatment, or are the surviving worms actually new strains that have been introduced due to migration of the black flies or of the parasite itself?”

In a third related study, a team led by Dr. Thomas Nutman at NIAID analyzed all the genes expressed (the transcriptome) and the proteins produced (the proteome) by O. volvulus and Wolbachia. As detailed on November 23, 2016, in mBio, the team identified hundreds of different proteins expressed at different points in the parasite’s lifestyle.

Taken together, these studies reveal critical information about the genomic diversity of the Onchocerca volvulus parasite. This new information may be useful for understanding drug resistance and finding new ways to treat river blindness.