Researchers in France have used proteomic techniques to try to understand the molecular mechanisms that enable a parasitic hairworm to "brainwash" its grasshopper host into committing suicide by jumping into water, where the adult worm is able to begin reproducing.
What they found is that the worm relies on mimetic proteins that are very similar to certain proteins found in insects in order to manipulate its host's behavior.
"The findings suggest that the adult worm alters the normal functions of the grasshopper central nervous system by producing certain 'effective' molecules," the authors conclude. "Our results suggest that the normal development of the host brain are seriously perturbed, possibly by an increase of apoptosis in the brain, causing a 'brain wash,' and by alteration of the visual cycle."
The study is believed to be the first to use proteomics to analyze changes in behavior. It could lead to proteomic study of other systems where the parasite manipulates the host for its own benefit. Examples of such systems include the Plasmodium falciparum malaria parasite, which alters something in humans so that their body odor attracts more mosquitoes, and the intestinal pin worm Enterobius vermicularis, which causes itching of its human host's anal area so that its eggs end up on fingers for easier transmission.
The Nematomorph hairworm, Spinochordodes tellinii, gets into its host grasshopper as aquatic larvae either when the grasshopper ingests the worm larvae with water, or when it ingests an insect larvae that has been infected by the worm larvae, explained David Biron and Frederic Thomas, the main authors of the grasshopper study, published last month in the Proceedings of the Royal Society B.
Once ingested by the grasshopper, the hairworm grows from a microscopic larva to a large worm whose size exceeds the length of the host by three to four times. The adult worm then induces its host, which is normally terrestrial, to seek water and to jump into it, thereby committing suicide. Once in the water, the worm then leaves the grasshopper through its rear and swims away to begin searching for a mate.
Thomas said that he and his research team at the Laboratory of Genetics and Evolution of Infectious Diseases in France's National Scientific Research Center in Montpellier decided to use proteomics to study behavioral manipulation because they wanted to better understand the molecular processes by which the grasshopper was induced to commit suicide by jumping into water.
"We can summarize the behavioral change as molecular," said Thomas. "Proteomics is the best way to study the molecular cross-talk between the host and parasite. We can study what the parasite and host are saying to each other [molecularly] before, during, and after behavioral manipulation."
The researchers captured grasshoppers infected with hairworms around a swimming pool in Avenes les Bains in southern France, which was located near a forest where adult hairworms were commonly found during the summer. A five-meter-wide concrete area between the forest and the swimming pool allowed for the direct observation of infected grasshoppers about to commit suicide.
The researchers captured grasshoppers that had jumped into the swimming pool. After the hairworms had emerged, they put the insects, which were generally still alive and moving, into dry, opaque plastic tumblers for an hour before dissecting them.
To serve as controls, the researchers captured uninfected grasshoppers from the forest and infected grasshoppers that had not yet shown signs of being behaviorally manipulated.
The researchers used 2D electrophoresis gels and mass specs to analyze the proteomes of each category of grasshopper and of the worms, which were taken out of the host's abdomen during dissection.
"We can summarize the behavioral change [suicide] as molecular. Proteomics is the best way to study the molecular cross-talk between the host and parasite. We can study what the parasite and host are saying to each other [molecularly] before, during, and after behavioral manipulation."
"What we found was the use of mimetic proteins," said Thomas. "The worm produced proteins that are very similar to the ones in insects. You can see in this that the parasite is learning the same language as the host."
According to Thomas and Biron, the mimetic proteins are probably important in a cascade of events that lead to the alteration of host behavior.
"Given the very large size of the adult hairworms S. tellinni, it is probably not too expensive for such a parasite to produce potent concentrations of mimetic and effective molecules acting directly on the CNS of its arthropod host to alter its behavior," the scientists wrote.
Biron added that the proteomic profiles of the host grasshopper differed in relation with its circadian cycle, its parasitic status, whether it had been manipulated, and whether a worm had emerged. For the parasite, differential proteomic expression was observed between parasitic and free-living stages, and between the period of manipulation and the period after emergence from the host.
Biron and Thomas said that they plan to follow up on this study by using proteomics to study other host-parasite systems where the host is manipulated by the parasite. Aside from studying other hairworms, another system they may study is the P. falciparum-carrying mosquito which is responsible for spreading malaria.
"It is very important to identify a biomarker of manipulation in order to better understand the dynamics of a disease transmitted by a vector," said Thomas. "It contributes to the general knowledge which helps to fight against the parasite."
Thomas said that he expects that molecular mimicry is a common strategy for a parasite to alter its host's behavior.
— Tien-Shun Lee ([email protected])