Periodic Parasites and Daily Host Rhythms

Abstract

Biological rhythms appear to be an elegant solution to the challenge of coordinating activities with the consequences of the Earth's daily and seasonal rotation. The genes and molecular mechanisms underpinning circadian clocks in multicellular organisms are well understood. In contrast, the regulatory mechanisms and fitness consequences of biological rhythms exhibited by parasites remain mysterious. Here, we explore how periodicity in parasite traits is generated and why daily rhythms matter for parasite fitness. We focus on malaria (Plasmodium) parasites which exhibit developmental rhythms during replication in the mammalian host's blood and in transmission to vectors. Rhythmic in-host parasite replication is responsible for eliciting inflammatory responses, the severity of disease symptoms, and fueling transmission, as well as conferring tolerance to antiparasite drugs. Thus, understanding both how and why the timing and synchrony of parasites are connected to the daily rhythms of hosts and vectors may make treatment more effective and less toxic to hosts.

Last-come, best served? Mosquito biting order and Plasmodium transmission

“…A periodic late afternoon increase in parasitaemia is also observed in the avian malaria system [41]. Such temporal variation may be a function of changes in the physiological, nutritional or immunological condition of the host [42][43][44].…”

“…A periodic late afternoon increase in parasitaemia is also observed in the avian malaria system [ 41 ]. Such temporal variation may be a function of changes in the physiological, nutritional or immunological condition of the host [ 42 – 44 ]. It may, however, also be an adaptive parasite strategy aimed at maximizing its own transmission [ 41 , 45 ].…”

Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms

“…Furthermore, the IDC schedule determines gametocyte age at the time-of-day the mosquito vector forages for blood [ 16 ] and gametocytes exhibit time-of-day variation in their infectiousness to mosquitoes [ 17 ]. For P. chabaudi, it appears that by completing the IDC at night—the time-of-day that nocturnal rodents forage—asexual replication is most successful and gametocytes are also at their most infective age when vectors blood feed [ 17 , 18 ].…”

“…This observation, coupled with recent discoveries of parasite control of the IDC schedule [ 25 – 27 ] suggests the degree of synchrony and the timing of the IDC are at least in part controlled by parasites. If so, it raises the possibility that a synchronous or asynchronous IDC are different parasite strategies that have evolved by natural selection because they enhance parasite fitness [ 18 ]. Synchronous or asynchronous replication is unlikely to have evolved as a consequence of abiotic environmental differences because P. berghei and P. yoelii are found in different climates ( P. berghei in the cool African highlands, P. yoelii in the warmer lowlands) [ 28 ].…”

“…inoculations of pure merozoites [ 21 ]) but synchrony is rapidly lost within a few cycles [ 20 ]. Intriguingly there are reports of synchronous P. berghei experimental infections in ground squirrels (with schizogony occurring at the start of the active, feeding, period which is the inverse of the schedule of P. chabaudi ) [ 18 , 32 ] and in infections of laboratory mice in which hosts were subjected to “summer-like” lighting conditions (extended light hours with wide wavelength light) [ 33 , 34 ]. Mammalian host physiological responses to summer photoperiods are thought to be controlled by the pineal gland [ 33 ], a regulator of host hormones such as melatonin, which has been implicated in modulating the rate of IDC development for synchronous species [ 35 ].…”