Although the parasite that causes schistosomiasis multiplies within aquatic snails for part of its life cycle, it finds one particular snail to be an inhospitable host. The unwelcoming snail is calledBiomphalaria glabrata, and it happens to possess a group of genes that gives it an eigh-fold decrease in the risk of schistosomiasis infection. These genes, recently discovered by researchers based atOregon State University, could lead to new drugs or novel means of interrupting the schistosomiasis parasite’s transmission cycle.
At present, the only drug that is used against schistosomiasis is praziquantel. Because it is being used ever more widely, praziquantel could become less and less effective if resistance develops in the schistosomiasis parasite. Alternative drugs, then, are much desired.
Besides contributing to drug development, the newly discovered parasite-resistant genes could be inserted into the species of snail that most commonly transmit schistosomiasis. Genetic engineering of this sort is already being evaluated as a means of curbing the spread of malaria. One line of investigation involves the controlled release of genetically modified mosquitoes in field trials.
Modifying snail populations to be resistant to the schistosomiasis parasite is currently not practical, but with the identification of parasite-resistant genes in Biomphalaria glabrata, an important first step has been taken.
The find was described March 16 in PLOS Genetics, in an article entitled, “Hyperdiverse Gene Cluster in Snail Host Conveys Resistance to Human Schistosome Parasites.” The article notes that a gene cluster called the Guadeloupe Resistance Complex may point to new drug targets or novel means of genetic manipulation.
“We map a natural parasite-resistance polymorphism from a Caribbean population of the snailBiomphalaria glabrata,” wrote the authors. “In independent experimental evolution lines, RAD genotyping shows that the same genomic region responds to selection for resistance to the parasiteSchistosoma mansoni. A dominant allele in this region conveys an eightfold decrease in the odds of infection.”
“Fine-mapping and RNA-Seq characterization reveal a <1Mb region, the Guadeloupe Resistance Complex (GRC), with 15 coding genes,” the authors continued. “The GRC resembles immune gene complexes seen in other taxa and is likely involved in parasite recognition.”
“These genes are the type that, in other animal species, help to recognize pathogens and trigger an immune response,” explained Michael Blouin, a professor of integrative biology in the OSU College of Science. “This is important new information. With further research we’ll learn more about the exact genetics and molecules that are involved as the parasite interacts with the host.”
With an impact on human health that rivals that of malaria, schistosomiasis has been called the neglected pandemic. It infects more than 200 million people in more than 70 countries, and is most common in areas with poor sanitation. It can cause chronic, lifelong disability, beginning with gastrointestinal problems and sometimes leading to liver damage, kidney failure, infertility, and bladder cancer.
For applications in the control of schistosomiasis, the GRC is an obvious target, the authors of the PLOS Genetics article concluded.
“Although genetic modification of snails is still in its infancy, the CRISPR nuclease system shows promise for fine-scale modification of even non-model species,” they added. “If the GRC genes initiate an immune signal cascade upon recognition of the parasite, future research could seek to manipulate snails such that this signal cascade is constitutively upregulated. The matching loci in the parasite, once they are identified, may also be targets for drugs or genetic manipulation.”