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

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Aidan J. O’Donnell ◽  
Sarah E. Reece
Keyword(s):  
Plasmodium Berghei ◽  
Time Of Day ◽  
Host Feeding ◽  
Ecological Interactions ◽  
Daily Rhythms ◽  
Development Cycle ◽  
Weak Evidence ◽  
Feeding Rhythms ◽  
Taxonomic Range ◽  
Malaria Species

Abstract Background Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious. Methods This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule of P. berghei and the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms. Results The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs on P. berghei; (ii) the IDC schedule of P. berghei is impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes. Conclusions Overall, host rhythms do not affect the performance of P. berghei and its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.

scholarly journals An essential amino acid synchronises malaria parasite development with daily host rhythms

2020 ◽  
Author(s):  
Kimberley F. Prior ◽  
Benita Middleton ◽  
Alíz T.Y. Owolabi ◽  
Mary L. Westwood ◽  
Jacob Holland ◽  
...  
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Blood Stage ◽  
Parasite Development ◽  
Host Feeding ◽  
Malaria Parasites ◽  
Disease Symptoms ◽  
Development Cycle ◽  
Feeding Rhythms ◽  
Blood Stage Malaria

SummaryThe replication of blood-stage malaria parasites is synchronised to the host’s daily feeding rhythm. We demonstrate that a metabolite provided to the parasite from the host’s food can set the schedule for Plasmodium chabaudi’s intraerythrocytic development cycle (IDC). First, a large-scale screen reveals multiple rhythmic metabolites in the blood that match the timing of the IDC, but only one - the amino acid isoleucine - that malaria parasites must scavenge from host food. Second, perturbing the timing of isoleucine provision and withdrawal demonstrate that parasites use isoleucine to schedule and synchronise their replication. Thus, periodicity in the concentration of isoleucine in the blood, driven by host-feeding rhythms, explains why timing is beneficial to the parasite and how it coordinates with host rhythms. Blood-stage replication of malaria parasites is responsible for the severity of disease symptoms and fuels transmission; disrupting metabolite-sensing by parasites offers a novel intervention to reduce parasite fitness.

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

2020 ◽  
Vol 287 (1932) ◽  
pp. 20200347
Author(s):  
Aidan J. O'Donnell ◽  
Kimberley F. Prior ◽  
Sarah E. Reece
Keyword(s):  
Time Of Day ◽  
Circadian Clocks ◽  
Host Feeding ◽  
Malaria Parasites ◽  
Disease Symptoms ◽  
Transmission Investment ◽  
Clock Proteins ◽  
Clock Mutant ◽  
Feeding Rhythms ◽  
Parasite Replication

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 clock-mutant 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.

scholarly journals Timing of host feeding drives rhythms in parasite replication

2017 ◽  
Author(s):  
Kimberley F. Prior ◽  
Daan R. van der Veen ◽  
Aidan J. O’Donnell ◽  
Katherine Cumnock ◽  
David Schneider ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Time Of Day ◽  
Circadian Oscillator ◽  
Parasite Development ◽  
Feeding Time ◽  
Host Immune System ◽  
Host Feeding ◽  
Malaria Parasites ◽  
Feeding Rhythms ◽  
The Brain

AbstractCircadian 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.Author summaryHow 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 reveal that rhythms associated with the time-of-day that hosts feed are responsible for the timing of rhythms in parasite development. Specifically, we altered host feeding time to phase-shift peripheral rhythms, whilst leaving rhythms driven by the central circadian oscillator in the brain unchanged. We found that parasite developmental rhythms remained synchronous but changed their phase, by 12 hours, to follow the timing of host feeding. Furthermore, our results suggest that parasites themselves schedule rhythms in their replication to coordinate with rhythms in glucose in the host’s blood, rather than have rhythms imposed upon them by, for example, host immune responses. Our findings reveal a novel relationship between hosts and parasites that if disrupted, could reduce both the severity and transmission of malaria infection.

scholarly journals Daily rhythms of both host and parasite affect antimalarial drug efficacy

2021 ◽  
Author(s):  
Alíz T Y Owolabi ◽  
Sarah E Reece ◽  
Petra Schneider
Keyword(s):  
Drug Treatment ◽  
Developmental Stage ◽  
Antimalarial Drug ◽  
Drug Sensitivity ◽  
Drug Efficacy ◽  
Time Of Day ◽  
Parasite Development ◽  
Daily Rhythms ◽  
Parasite Plasmodium

Abstract Background and objectives Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test if the daily rhythms of hosts, parasites, and their interactions, affect sensitivity to the key antimalarial, artemisinin. Methodology Asexual malaria parasites develop rhythmically in the host’s blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity. Results We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned. Conclusions and implications Parasite rhythms influence drug sensitivity in vivo. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach. Lay Summary We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites’ developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.

Plasmodium berghei and Plasmodium chabaudi chabaudi: development of simple in vitro erythrocyte invasion assays

Parasitology ◽  
1992 ◽  
Vol 105 (3) ◽  
pp. 355-362 ◽  
Author(s):  
J. McNally ◽  
S. M. O'donovan ◽  
J. P. Dalton
Keyword(s):  
Plasmodium Berghei ◽  
Plasmodium Chabaudi ◽  
Rodent Malaria ◽  
Erythrocyte Invasion ◽  
Malaria Species ◽  
Invasion Assays

SUMMARYErythrocyte invasion assays are described for two species of rodent malaria, namely Plasmodium berghei and P. c. chabaudi. These invasion assays are simple, are carried out using a candle jar and allow a number of assays to be performed simultaneously. Our results demonstrate that both rodent malaria species show an in vitro preference for reticulocytes although the preference of P. c. chabaudi for these cells is not as marked as that of P. berghei. The details of our invasion assays and our results obtained are discussed.

scholarly journals Circadian Regulation of Cardiac Physiology: Rhythms That Keep the Heart Beating

2020 ◽  
Vol 82 (1) ◽  
pp. 79-101 ◽  
Author(s):  
Jianhua Zhang ◽  
John C. Chatham ◽  
Martin E. Young
Keyword(s):  
Time Of Day ◽  
Active Period ◽  
Cardiac Physiology ◽  
Daily Rhythms ◽  
Heart Beating ◽  
Endocrine Factors ◽  
Energetic Demand ◽  
Key Aspects ◽  
Food Intake Patterns ◽  
By Products

On Earth, all life is exposed to dramatic changes in the environment over the course of the day; consequently, organisms have evolved strategies to both adapt to and anticipate these 24-h oscillations. As a result, time of day is a major regulator of mammalian physiology and processes, including transcription, signaling, metabolism, and muscle contraction, all of which oscillate over the course of the day. In particular, the heart is subject to wide fluctuations in energetic demand throughout the day as a result of waking, physical activity, and food intake patterns. Daily rhythms in cardiovascular function ensure that increased delivery of oxygen, nutrients, and endocrine factors to organs during the active period and the removal of metabolic by-products are in balance. Failure to maintain these physiologic rhythms invariably has pathologic consequences. This review highlights rhythms that underpin cardiac physiology. More specifically, we summarize the key aspects of cardiac physiology that oscillate over the course of the day and discuss potential mechanisms that regulate these 24-h rhythms.

scholarly journals Quantitative analysis of repaired and unrepaired damage to trilobites from the Cambrian (Stage 4 - Drumian) Iberian Chains, NE Spain

2018 ◽  
Author(s):  
Stephen Pates ◽  
Russell DC Bicknell ◽  
Allison C. Daley ◽  
Samuel Zamora
Keyword(s):  
Process Analysis ◽  
Healing Process ◽  
Ecological Interactions ◽  
Deep Time ◽  
Formation Stage ◽  
Weak Evidence ◽  
Stage 4 ◽  
Repair Mechanisms ◽  
Long Time ◽  
Selection For

Repaired fossil skeletons provide the opportunity to study predation rates, repair mechanisms, and ecological interactions in deep time. Trilobites allow the study of repaired damage over long time periods and large geographic areas due to their longevity as a group, global distribution, and well-preserved mineralized exoskeletons. Repair frequencies on trilobites from three sites representing offshore marine environments in the Iberian Chains (Spain) show no injuries on 45 complete redlichiid thoraces from Minas Tierga (Huérmeda Formation, Cambrian Series 2, Stage 4), or 23 complete Eccaparadoxides pradoanus thoraces from Mesones de Isuela (Murero Formation, Cambrian Series 3, Drumian). Ten injuries on 69 E. pradoanus thoraces from Purujosa (Murero Formation, Cambrian Series 3, Drumian) were noted. There is no evidence for laterally asymmetric predation or size selection on the trilobites in this study. Weak evidence for selection for the rear of the thorax is documented. A series of injured trilobites illustrates four stages of the healing process. Analysis of injury locations and frequency suggests that injuries to these trilobites are predatory in origin. Semilandmark analysis of previously described exoskeletons with unrepaired damage assigned to the ichnotaxon Bicrescomanducator serratus alongside newly collected damaged exoskeletons from Purujosa (Mansilla and Murero Formations, Stage 5, Drumian), Mesones de Isuela (Murero Formation, Drumian), and Minas Tierga (Huérmeda Formation, Stage 4) found that shapes of biotic and abiotic breaks could not be distinguished.

scholarly journals Dosing Time Matters

2019 ◽  
Author(s):  
Marc D. Ruben ◽  
David F. Smith ◽  
Garret A. FitzGerald ◽  
John B. Hogenesch
Keyword(s):  
Clinical Practice ◽  
Time Of Day ◽  
Diagnosis And Treatment ◽  
Daily Rhythms ◽  
Human Trials ◽  
Human Genes ◽  
Insight Into ◽  
Time Of Administration

AbstractTrainees in medicine are taught to diagnose and administer treatment as needed; time-of-day is rarely considered. Yet accumulating evidence shows that ∼half of human genes and physiologic functions follow daily rhythms. Circadian medicine aims to incorporate knowledge of these rhythms to enhance diagnosis and treatment. Interest in this approach goes back at least six decades, but the path to the clinic has been marked by starts, stops, and ambiguity. How do we move the field forward to impact clinical practice? To gain insight into successful strategies, we studied the results of more than 100 human trials that evaluated time-of-administration of drugs.

scholarly journals Comparison of daily rhythms of oxygen metabolites and serum barrier to oxidation in domestic animals

2011 ◽  
Vol 6 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Claudia Giannetto ◽  
Francesco Fazio ◽  
Stefania Casella ◽  
Anna Assenza ◽  
Simona Marafioti ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Time Of Day ◽  
Reactive Oxygen Metabolites ◽  
Daily Rhythms ◽  
Mammal Species ◽  
Thoroughbred Horses ◽  
Natural Photoperiod ◽  
Daily Rhythmicity ◽  
Anti Oxidant ◽  
Oxygen Metabolites

AbstractThe aim of this study was to compare the daily rhythm of reactive oxygen metabolites (hydroperoxides), and serum barrier to oxidation in five different mammal species. Five female Comisana sheep, five female Maltese goats, five female Bruna cows and five female Thoroughbred horses were housed separately in boxes equipped with an opening window and five female Blue Vienna rabbits were individually housed in metallic cages. All animals were kept under natural photoperiod and indoor environmental conditions. Blood samples were collected every 3 h over a 48 h period for the assessment of hydroperoxides, antioxidant barrier (Oxy-ads) and thiol-antioxidant barrier (SHp). A two-way for repeated measures ANOVA showed a significant effect of time of day and different species on all studied parameters. Daily rhythmicity of hydroperoxides, Oxy-ads and SHp were observed in all studied species. Nocturnal acrophases were observed in sheep, goats and rabbits, diurnal acrophases were observed in cattle and horse. We conclude that there is a synergism of the daily rhythms of hydroperoxides and anti-oxidant power in the different species studied, and that this synergism is typical of each species.

Sign in / Sign up

Export Citation Format

Share Document