Abstract
Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host’s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host’s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new arena for studying host-parasite-vector coevolution and has broad implications for applied bioscience.
Highlights
The discovery of daily rhythms in parasites dates back to the Hippocratic era and a taxonomically diverse range of parasites display rhythms in development and several behaviours
How cycles of asexual replication by malaria parasites are coordinated to occur in synchrony with the circadian rhythms of the host is a long-standing mystery
We altered host feeding time to phase-shift peripheral rhythms, whilst leaving rhythms driven by the central circadian oscillator in the brain unchanged
Summary
The discovery of daily rhythms in parasites dates back to the Hippocratic era and a taxonomically diverse range of parasites (including fungi, helminths, Coccidia, nematodes, trypanosomes, and malaria parasites [1,2,3,4,5,6]) display rhythms in development and several behaviours. How rhythms in many parasite traits are established and maintained remains mysterious, despite their significance, as these traits underpin the replication and transmission of parasites [7]. Endogenous circadian oscillators (“clocks”) involve transcription-translation feedback loops whose timing is synchronised to external cues, such as light-dark and feeding-fasting cycles [9,10] but there is generally little homology across taxa in the genes underpinning oscillators. Convergent, evolutionary origins for circadian oscillators is thought to be explained by the fitness advantages of being able to anticipate and exploit predictable daily changes in the external environment, as well as keeping internal processes optimally timed [11,12]. The 2017 Nobel Prize in Physiology/Medicine recognises the importance of circadian oscillators [13,14]
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