Host circadian clocks do not set the schedule for the within-host replication of malaria parasites

Circadian clocks coordinate organisms’ activities with daily cycles in their
environment. Parasites are subject to daily rhythms in the within-host environment,
resulting from clock-control of host activities, including immune
responses. Parasites also exhibit rhythms in their activities: the timing of
within-host replication by malaria parasites is coordinated to host feeding
rhythms. Precisely which host feeding-related rhythm(s) parasites align with
and how this is achieved are unknown. Understanding rhythmic replication
in malaria parasites matters because it underpins disease symptoms and
fuels transmission investment. We test if rhythmicity in parasite replication
is coordinated with the host’s feeding-related rhythms and/or rhythms
driven by the host’s canonical circadian clock. We find that parasite rhythms
coordinate with the time of day that hosts feed in both wild-type and clockmutant
hosts, whereas parasite rhythms become dampened in clock-mutant
hosts that eat continuously. Our results hold whether infections are initiated
with synchronous or with desynchronized parasites.We conclude that malaria
parasite replication is coordinated to rhythmic host processes that are independent
of the core-clock proteins PERIOD 1 and 2;most likely, a periodic nutrient
made available when the host digests food. Thus, novel interventions could
disrupt parasite rhythms to reduce their fitness, without interference by host
clock-controlled homeostasis.