Host manipulation by parasites

By Ching Nam Wong (Jimmy)

Parasites are organisms that depend on another host organism to support them with the necessary resources. In the process, parasites usually cause disease and decrease host fitness, while completing parasite life cycles and transmitting to the next host. 

Many parasites can manipulate their hosts, usually by inducing changes in host phenotypes in ways that benefit the parasite species’ fitness; this is called host manipulation. This usually means that after a parasite infects its host, parasite genes induce changes in host phenotype by a series of biochemical pathways which help the parasite to complete its life cycle, increasing parasite dispersal and transmission rate. For example, Toxoplasma gondii has to transmit from rats (intermediate host) to cats (definite host). To make this jump, T. gondii reverse rats’ innate aversion to cat odor into attraction to cat odor by host manipulation, leading to higher dispersal rate of T.gondii while the rats suffer the consequences (M Berdoy, J P Webster & D W Macdonald, 2000).

But how did these parasites manipulate their hosts? The mechanisms behind host manipulation is one of the least understood areas in parasite research. Although we know parasites can change their host behavior pattern; change host phenotype; and manifest new behaviors/phenotypes, we have limited knowledge about the exact pathways by which these changes occur. Some parasites – like cestodes within fish hosts – may secrete neurological substances (eg. serotonin, dopamine), while other parasites interfere with host biochemical pathways and hormones, all of which lead to alteration of host behavior. However, it is difficult to distinguish between pathways. For example, trematodes of the genus Schistosoma secrete opioid peptides into their hosts that suppress the host immune system while also influencing host neurological functions. Consequently, identifying the opioid peptide’s original function is difficult, and these processes are easily mixed up, making them hard to study  (M Kavaliers, D D Colwell & E Choleris, 1999). 

From a survival point of view, host manipulation by parasites should limit the induction cost (resource cost of host manipulation) while maximizing parasite transmission and dispersion. Therefore, it is in the parasite’s best interest to make use of existing pathways or niches of their hosts so as not to overly compromise host fitness. For example, malaria-infected mosquitos naturally have reduced fecundity, but if these mosquitos are allowed to feed on more hosts per unit time their fecundity will recover back to normal, while still readily transmitting malaria (Thierry Lefèvre et al., 2009).  

Even though there are numerous mechanisms of host manipulation, the logical process behind them is the same: there are substances that have a downstream effect on host phenotype or behavior, and the concentration of these substances can be changed following a parasite infection. Theoretically, parasites can synthesize these substances in the form of host mimic proteins and release them into hosts. However, in reality this is rarely done, as parasites usually just interfere with existing pathways within host cells to either up- or down-regulate substances. This has a domino effect on the whole biochemical cascade, eventually leading to phenotype changes that favor parasite transmission. This is a “cheaper” way to minimize induction cost. However, the point at which different parasites interfere with existing biochemical pathways is still a mystery that requires more research to find out. Discovering unusual serotonin levels in infected hosts is perhaps only a small step within a long biochemical cascade yet to be discovered  (Poulin, 2010).

Host manipulation did seem to be a great survival strategy; changing host phenotype or behavior can greatly increase parasite dispersion and fitness. However, how do we quantify the efficacy of different host manipulation strategies? Host manipulation strategies vary extensively, from changing host in color to changes in host food preference – it is almost impossible to put them on the same scale. As a consequence, the effectiveness of host manipulation is measured by the net increase in the transmission success of the manipulating parasite. For example, a trematode parasite induces 4x changes in the frequency of conspicuous swimming action in infected fish (intermediate host). This eventually leads to a 30x increase in predation rate by birds (definite host) (Kevin Lafferty & Kimo Morris, 1996). Although not as extreme as the previous example, most parasites research shows host manipulation generally have a significant positive effect on parasite dispersion, with parasite-infected hosts having 25-35% more chance of being taken up by their predators (F. Thomas et al., 1998).

Although host manipulation did seem beneficial to parasites, we have to acknowledge the fact that all these experiments are carried out in a laboratory environment with the predator being the only suitable definite host for the parasite, the benefits of host manipulation seems too exaggerated. In the real world with complex food webs, there are usually multiple predators targeting the same prey, hence parasite transmission can go wrong when the parasite is being ingested by a non-compatible host, reaching a “dead-end”. For example, Curtuteria australis is a parasite that must be transferred from cockle (intermediate host) to birds (definite hosts). Normally cockles will bury themselves in intertidal sediments, but C. australis manipulates cockles to sit on the surface instead, leading to cockles being 5-times more likely to be eaten by birds (Kim N. Mouritsen & Robert Poulin, 2003). However, parasite-manipulated cockles are also more likely to be eaten by a dead-end host, e.g. fish and whelks, than if no manipulation were performed, given that the predation rate of cockles to birds is quite low in the community. In a fitness point of view, parasites stuck in a dead-end host are no different than failing parasite transmission in a non-manipulated cockle; therefore in comparison, host manipulation can be advantageous, but how big this advantage is can be questionable. If there were more fish, more whelks, and fewer birds, this advantage can be negligible. Therefore, in real-life host manipulative parasites can thrive in some communities but constantly fail in others, as benefits of host manipulation depend on the number and population of different predators present in the environment. 

Overall, how parasites manipulate their hosts is a complex topic and our current understanding about it is limited. However, it is fascinating how these host manipulating strategies in parasites evolve and operate. Hopefully, future research involving proteome and DNA analysis on parasites may shed more light on how different parasites work.

References:

F. Thomas, F. Renaud, T Demee & R. Poulin. (1998) Manipulation of host behaviour by parasites: ecosystem engineering in the intertidal zone? Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1689167/.

Kevin Lafferty & Kimo Morris. (1996) Altered Behavior of Parasitized Killifish Increases Susceptibility to Predation by Bird Final Hosts. Available from: https://www.researchgate.net/publication/242100394_Altered_Behavior_of_Parasitized_Killifish_Increases_Susceptibility_to_Predation_by_Bird_Final_Hosts.

Kim N. Mouritsen & Robert Poulin. (2003) Parasite-induced trophic facilitation exploited by a non-host
predator: a manipulator’s nightmare. Available from: https://www.otago.ac.nz/parasitegroup/PDF%20papers/MouritsenPoulin2003-IJP.pdf.

M Berdoy, J P Webster & D W Macdonald. (2000) Fatal attraction in rats infected with Toxoplasma gondii. Available from: https://pubmed.ncbi.nlm.nih.gov/11007336/.

M Kavaliers, D D Colwell & E Choleris. (1999)  Parasites and behavior: an ethopharmacological analysis and biomedical implications. Available from: https://pubmed.ncbi.nlm.nih.gov/10580316/.

Poulin, R. (2010) Parasite Manipulation of Host Behavior.

Thierry Lefèvre, Shelley A Adamo, David G Biron & Dorothée Missé. (2009) Invasion of the body snatchers: the diversity and evolution of manipulative strategies in host-parasite interactions. Available from: https://pubmed.ncbi.nlm.nih.gov/19289190/.