Disrupting rhythms in Plasmodium chabaudi: costs accrue quickly and independently of how infections are initiated

Aidan J O’Donnell,Nicole Mideo,Sarah E Reece

doi:10.1186/1475-2875-12-372

Aidan J O’Donnell, Nicole Mideo + Show 1 more

Open Access

https://doi.org/10.1186/1475-2875-12-372

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Abstract

BackgroundIn the blood, the synchronous malaria parasite, Plasmodium chabaudi, exhibits a cell-cycle rhythm of approximately 24 hours in which transitions between developmental stages occur at particular times of day in the rodent host. Previous experiments reveal that when the timing of the parasite’s cell-cycle rhythm is perturbed relative to the circadian rhythm of the host, parasites suffer a (~50%) reduction in asexual stages and gametocytes. Why it matters for parasites to have developmental schedules in synchronization with the host’s rhythm is unknown. The experiment presented here investigates this issue by: (a) validating that the performance of P. chabaudi is negatively affected by mismatch to the host circadian rhythm; (b) testing whether the effect of mismatch depends on the route of infection or the developmental stage of inoculated parasites; and, (c) examining whether the costs of mismatch are due to challenges encountered upon initial infection and/or due to ongoing circadian host processes operating during infection.MethodsThe experiment simultaneously perturbed the time of day infections were initiated, the stage of parasite inoculated, and the route of infection. The performance of parasites during the growth phase of infections was compared across the cross-factored treatment groups (i e, all combinations of treatments were represented).ResultsThe data show that mismatch to host rhythms is costly for parasites, reveal that this phenomenon does not depend on the developmental stage of parasites nor the route of infection, and suggest that processes operating at the initial stages of infection are responsible for the costs of mismatch. Furthermore, mismatched parasites are less virulent, in that they cause less anaemia to their hosts.ConclusionIt is beneficial for parasites to be in synchronization with their host’s rhythm, regardless of the route of infection or the parasite stage inoculated. Given that arrested cell-cycle development (quiescence) is implicated in tolerance to drugs, understanding how parasite schedules are established and maintained in the blood is important.

Highlights

In the blood, the synchronous malaria parasite, Plasmodium chabaudi, exhibits a cell-cycle rhythm of approximately 24 hours in which transitions between developmental stages occur at particular times of day in the rodent host
The aims of the experiment reported here were to validate that the performance of P. chabaudi is negatively affected by mismatch to the host circadian rhythm, test whether the costs of mismatch are influenced by the route of infection or the developmental stage of inoculated parasites, and to examine whether the costs of mismatch are due to challenges encountered upon initial infection or to processes operating throughout the infection
The results confirm that mismatch to host rhythms is costly for parasites, reveal that this phenomena does not depend on the developmental stage of parasites nor the route of infection, and suggest that processes operating at the initial stages of infection are responsible for the costs of mismatch

Summary

Introduction

The synchronous malaria parasite, Plasmodium chabaudi, exhibits a cell-cycle rhythm of approximately 24 hours in which transitions between developmental stages occur at particular times of day in the rodent host. The reduced performance of schedule mismatched parasites observed in [10] does not reveal whether coordination between parasite cell-cycle progression and the host circadian rhythm is controlled by parasites or hosts or both This remains an important route of future investigation which will be facilitated by better characterisation of the costs of mismatch. Parasite developmental stages may vary in their sensitivity to peaks in the rhythms of innate immune defences in the blood/spleen or the nutritional requirements of different stages may not be met at certain times of day These time-of-day dependent challenges could affect parasites as they enter the host (if, for instance, low densities of parasites are vulnerable, or these processes operate at the site of infection) and/or during every cycle as infections progress. A clear prediction is that if mismatch causes costs in the initial phase of infections there will be fewer parasites appearing in the blood and if costs are due to ongoing processes, there will be differences in multiplication rate throughout infections

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