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Hungry parasites: when hosts eat, their parasites do too

If you want to control your parasite infection, the time that you eat may be the answer. A new study has found that the time of day that hosts eat affects the daily activities of their malaria parasites.

As human beings, we follow a very repeatable pattern every day: sleep, work, eat, repeat... Most of our biological processes also follow daily rhythms. This includes rhythms in activity, body temperature, food intake, metabolism etc. To know what and when to do things each day, we take cues from our environment, mainly the sun, to set the timing of our internal clocks. We need these “circadian” clocks for survival and reproduction because they allow us to synchronise our biological processes with changes in our environment. 

Host Mealtimes affects the Malaria Lifecycle

Our biological rhythms are so powerful that is perhaps no surprise that they are open to be exploited. The parasites that live in or on us – and many other life forms - are also subjected to their host’s daily rhythms and several studies have now begun to reveal how this affects them4. Our lab have published a new study demonstrating that the timing of host’s meals affects the timing of malaria parasites’ cycle of replication. Malaria parasites can only complete their life cycle by infecting two successive hosts: vertebrate hosts such as humans or other animals, and female mosquitoes, which then spread the disease.

Plasmodium chabaudi inside red blood cells
Plasmodium chabaudi inside red blood cells - Image Credit: Kim Prior

Human Frontier Science Program (HFSP) funding was a vital step in getting our project off the ground. We used a mouse model system, to show that when the mice’s mealtime changed, the parasites living inside them altered the timing of their lifecycle, including when they infected red blood cells and when the parasite population multiplied.

Why is Eating Important?

So, why is eating important for parasite rhythms? We found that increasing blood glucose levels after mealtimes, coincided with the time at which the most metabolically active parasite forms were present in the blood. This suggests that parasites may use glucose as a food source and cannot complete their development without it.

Alternatively, parasites might be using host mealtimes as an environmental time cue, just as we use the sun to time our rhythms. If at certain times of the day the parasite’s cycle of replication is more vulnerable to their host’s immune system, then it makes sense that parasites should schedule their rhythm to avoid the most damaging immune attacks. If this is the case then meal times might just be a convenient way of sensing their hosts overall biological rhythms and boosting their chances of survival. 

Influencing Immune Responses

However, it was once thought that parasites could not organise their own rhythms and were simply reacting to rhythms in their host’s immune response. Our experiments suggest this is not the case. By measuring host cytokines, a marker of the immune response during infections, we revealed that it is actually the parasites that influence the host’s immune response rhythms. This means that parasites are firmly in the driving seat with an active role in shaping our immune response rather than simply trying to evade it.

Interfering with Parasite Rhythms

Understanding what drives the timing of parasite rhythms is important. Like us, parasites get jet lag, and their numbers suffer when the timing of their rhythms is out-of-sync with their hosts3. If we could interfere with parasite rhythms we may be able to reduce the severity and spread of malaria infection. Disrupting the link between eating and parasite timing – perhaps through host diet, or via drugs that manipulate the biological pathways involved in time-keeping – could lead to a new strategy for tackling malaria.

With the number of malaria cases steadily increasing and reports of growing drug and insecticide resistance, we need now more than ever to find new ways to control and eventually eliminate malaria. Fears of a resurgence in global malaria cases are prompting further investment in research, including the additional $1bn investment by the Bill & Melinda Gates Foundation.

Other Infections

Our work focuses on malaria parasites, but rhythms matter to other parasites too, for example in Lymphatic filariasis, a parasitic disease caused by roundworms and spread by black flies and mosquitoes2. Rhythms may also play a role in establishing infections in new hosts, such as Salmonella passing from food to rodents1,5,6. It is possible that bacteria and viruses may also have a similar type of host-parasite interaction, where rhythms play an important role in disease severity and spread.

Understanding how differences in timing affect both parasites and hosts, as well as gaining insights into the biological mechanisms controlling their rhythms, could give us the tools to tackle many types of infection. 

Related Links

Prior KF, van der Veen DR, O’Donnell AJ, Cumnock K, Schneider D, Pain A, Subudhi A, Ramaprasad A, Rund SSC, Reece SE. Timing of host feeding drives rhythms in parasite replication. 2018. PLoS Pathog, 14:e1006900. doi: 10.1371/journal.ppat.1006900.

Other references

  1. Bellet MM, Deriu E, Lui JZ, Grimaldi B, Blaschitz C, Zeller M, Edwards RA, Sahar S, Dandekar S, Baldi P, George MD, Raffatellu M, Sassone-Corsi P. Circadian clock regulates the host response to Salmonella. 2013. PNAS, 110, 9897-9902.
  2. Hawking F. The 24-hour periodicity of microfilariae: biological mechanisms responsible for its production and control. 1967. Proc R Soc B, 169, 59-76.
  3. O’Donnell AJ, Schneider P, McWatters HG, Reece SE. Fitness costs of disrupting circadian rhythms in malaria parasites. 2011. Proc R Soc B, 278, 2429-2436.
  4. Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi JS, Figueiredo LM. Trypanosoma brucei metabolism is under circadian control. 2017. Nat Microbiol, 13, 17032.
  5. Roden LC, Ingle RA. Lights, rhythms, infection: The role of light and the circadian clock in determining the outcome of plant-pathogen interactions. 2009. The Plant Cell, 21, 2546-2552.
  6. Shirasu-Hiza MM, Dionne MS, Pham LN, Ayres JS, Schneider DS. Interactions between circadian rhythm and immunity in Drosophila melanogaster. 2007. Curr Biol, 17, 353-355.