Parasites and host behaviour: Co-evolution from genotype to phenotype

Have you ever considered the possibility that you are not entirely in control of your own mind and behaviour? Well, you should. Tiny parasites living inside human bodies, and other animals, have been shown to make small yet significant adjustments to personality, mood, and behaviour. Many parasites are able to modify the behavior of the organisms they live on (or in), their so-called hosts, in ways that are seemingly good for the parasite but bad for the host. Infected animals can do such weird things as drowning themselves or allowing themselves to be eaten. This makes no sense to anyone but the parasites which jump between different hosts in their life cycle, or get spread to new environments. One organism called Euhaplorchis californiensis occur as cysts on the brain of California killifish and causes the fish to seek to the water surface and lose their normal fear of predatory birds, whose intestines provide the next environment for the parasites. This project tests the novel hypothesis that in fact both birds and parasites benefit from this interaction. Results from the project suggest that the intestinal worms would cause little or no harm to the birds, who instead benefit from a supply of easy-to-catch meals. One might even say that the birds use the parasites as biological warfare against their prey, instead of trying to get rid of them. Exactly how the parasite manipulates the behavior of its fish host is also a topic. It is known that parasites in some cases acquire genes from their hosts, and these genes may help parasites to avoid recognition by the host immune system. We have shown that parasites in their behaviour-manipulating stafe overexpress an enzyme which metabolises the essential amino acid tryptophan. Draining the local environment of tryptophan is a mechanism to inhibit immune function utilised by for instance cancer cells and the mammalian placenta, but multicellular organisms has not previously been shown to do this.Finally, we are interested in seeing if some hosts are easier to manipulate than others. To explore the latter question we have utlised zebrafish with consistent differences in stress coping style. A most interesting result is that parasite encounters leave a lasting impression on brain and behavior also on hosts that are resistant. This thickens the plot. We have discovered that parasites can manipulate host phenotypes even when no longer being present in the body. They can just drop by to pay a short visit and leave. Their short visit activates the body’s defence system which rapidly kicks the parasites out. Yet, a ghost of this parasite has left a subtle impression. Observing Medaka, the common pet fish known as Japanese Rice fish, we have now documented lasting behavioural effects in hosts resisting infection. Despite repeated attempts to infect these fish, they resisted infection. Yet, the infection attempts resulted in the fish developing a more social personality and becoming more physically active. In consequence, important aspects of animal and human behaviour can in theory be dictated by known and unknown parasite encounters. For context, more than half of the species on earth are parasites, and humans are presently known to harbour some 400 out of these. But the question that arises now is not how many successfully infect us, but rather how many we simply encounter and defeat, but still mess with our minds. Individual behavioural profiles ("personalities") may thus be to a large degree governed by infections that does not yield any classical signs of disease. The results from this project may thus be relevant to the emerging understanding of how interactions between the immune and nervous system in shaping individual health and stress coping profiles.

The project suggests a resolve to a long standing debate, by showing that parasites indeed directly affect the host nervous system, but the same mechanism doubles as immune defense and may indeed have originally evolved as such. Demonstrating this novel principle of neuroimmune crosstalk and consequences thereof will impel the research front to move significantly forward in this field. Another tangible outcome is the establishing of a pipeline for genome-wide identification of candidate genes for host phenotypic manipulation. A policy of open-access sharing of multi-omics datasets is established, and provides a resource for integrative data exploration by the scientific community at large. This will lay the grounds for developing new model systems amenable to experimental study, and call forth further studies towards the true impact of parasites and pathogens on behaviour and neurobiology both in natural ecosystems and, tentatively, in the human society.

This project builds on and interacts with the recently funded RCN FRIPRO project entitled: Parasite control of host behaviour: Revealing a neurobiological mechanism for active manipulation (NEUROPAR, 2015-2018). The purpose of this proposal is to facilitate the formation of an internationally competitive research group in the field of host-parasite systems biology. The introduction and testing of several fundamentally new concepts regarding evolutionary drivers and molecular-genetic mechanisms for parasite control of host phenotype is described. A specifc aim is to identify genes coding for neuroactive signalling substances in the genome of the endoparasitic trematode Euhaplorchis californiensis, and thereby test a novel hypothesis: That parasites may acquire the ability to manipulate host phenotype by molecular mimicry or sequestration of specific host genes, as is known to occur for the purpose of immune evasion. A pipeline for genome-wide identification of candidate genes and screening for close hits in the genomes vertebrate hosts will be developed, which in turn will lay the grounds for testing another arcane idea: One main evolutionary driver for parasite mediated trophic transmission could be the energetic benefit of the final host, in addition to increased parasite fitness. In other words, I hypothesize that parasitized animals demonstrating decreased anti-predator behavior fulfil the extended phenotype not only of the parasite but that of the predator. The project has subsidiary aims, in order to not depend to heavily on this untested idea. A zebrafish and a rodent-Toxoplasma gondii model will also be established to test the hypothesis that inherently reactive (= more flexible) phenotypes are more susceptible to manipulation. Finally, field and laboratory studies of a Nordic species (Arctic char, Salvelinus alpinus) are proposed in order to reveal a possible novel case of manipulation of host physiology.