Biology subjects

Reece, S. E.

Publications and source records attributed to Reece, S. E..

14 recordsLinked to original sources

bioRxiv2026

Keeping time with the host: reconstructing the developmental rhythms of malaria parasites

Theory predicts that pathogenic organisms benefit from aligning to host circadian rhythms, but observable data provide an incomplete picture of infection rhythms. Models are needed to reconstruct unobservable dynamics and uncover fitness impacts, challenges typified in malaria infections. Malaria parasites often synchronize their development to multiples of 24 hours and reschedule their developmental rhythms following perturbation. Yet it remains uncertain how parasites reschedule--including any cost to parasite multiplication rates--due to the diffculty of detecting parasites in all phases of their development. As parasites mature, the red blood cells they occupy adhere to blood vessel walls (sequestration, an immune evasion tactic) where they cannot be readily sampled. Existing methods cannot determine sequestration timing in vivo nor how that timing varies when misaligned to within-host environments. To address these challenges, we fit a mathematical model tracking parasite development and sequestration to high-resolution time series from the rodent malaria parasite Plasmodium chabaudi. We show that parasites hasten late development--but not sequestration--to realign with host rhythms. That rescheduling reduces multiplication rates, a result only apparent from model-reconstructed dynamics. Our novel approach recovers the timing of development and sequestration, providing insight into the consequences of circadian rhythms for parasite fitness.

ecology↗

bioRxiv2025

Malaria parasites adjust liver stage development to synchronise the blood stage of infection with host daily rhythms.

Synchronised multiplication of Plasmodium parasites within red blood cells causes periodic malaria fevers. Aligning blood-stage development with the vertebrate hosts feeding-fasting rhythm facilitates within-host survival and between-host transmission. We use the rodent model Plasmodium chabaudi to test when, following development in the liver, the blood stage of infection begins. We find egress from the liver into the blood is aligned with the time of day of rhythmic host feeding, but only in wild type hosts, with egress occurring after a fixed period of pre-erythrocytic development in hosts without a functional canonical clock. However, perturbing the duration over which parasites enter the bloodstream does not affect their multiplication rate in the first few IDCs, suggesting fitness benefits from timing egress anticipates rhythmic challenges or opportunities later in the infection.

microbiology↗

bioRxiv2025

Biting time of day in malaria mosquitoes is modulated by nutritional status

BackgroundTransmission of vector-borne pathogens follows daily rhythms, occurring at the time of day that vectors forage for blood. Control measures such as insecticide-treated bed nets (ITNs) have been particularly successful for reducing malaria transmission, because they exploit the nocturnal biting behaviour of the Anopheles spp. that vector malaria. However, shifts in biting behaviour to earlier or later hours when people are unprotected can undermine the efficacy of ITNs. Despite the implications for malaria transmission, the mechanisms underlying these shifts remain poorly understood. Because food availability mediates activity and foraging rhythms, and ITNs block access to human blood as a food source, we hypothesized that nutritional deprivation could cause mosquitoes to shift their biting behaviour to earlier or later in the diel cycle. MethodsWe provided female Anopheles gambiae s.l. mosquitoes with a blood meal on day 3 post-emergence, and access to one of three feeding treatments that varied in nutritional resources: (i) 0.5% sucrose, (ii) 10% sucrose, or (iii) 10% sucrose plus an additional blood meal on day 6. We released mosquitoes into a semi-field system on day 10 with human-mimic traps to investigate how food availability impacted the time of day that mosquitoes host seek. ResultsNutritional resources determine both the likelihood and time of day that host seeking occurs. Specifically, low-resourced mosquitoes were 2-3 fold more likely to host seek overall, and 5-10 fold more likely to host seek at an earlier time of day than well-resourced mosquitoes (fed 10% sucrose with and without an additional blood meal), which predominantly sought a host in the second half of the night time. ConclusionsWe reveal that mosquito nutritional condition drives plasticity in biting time of day, suggesting it is an underappreciated contributor to residual malaria transmission. Furthermore, our results suggest that targeting mosquito nutrition (e.g. sugar-baited traps) could influence mosquito behaviour in ways that affect the success of ITNs. More broadly, understanding the drivers of biting time of day variation is crucial for the future success of vector control tools and controlling malaria transmission.

ecology↗

bioRxiv2024

How to quantify developmental synchrony in malaria parasites

Malaria infections represent an iconic example of developmental synchrony, where periodic fevers can result when the population of parasites develops synchronously within host red blood cells. The level of synchrony appears to vary across individual hosts and across parasite species and strains, variation that--once quantified--can illuminate the ecological and evolutionary drivers of synchrony. Yet current approaches for quantifying synchrony in parasites are either biased by population dynamics or unsuitable when population growth rates vary through time, features ubiquitous to parasite populations in vitro and in vivo. Here we develop an approach to estimate synchrony that accounts for population dynamics, including changing population growth rates, and validate it with simulated time series data encompassing a range of synchrony levels in two different host-parasite systems: malaria infections of mice and human malaria parasites in vitro. This new method accurately quantifies developmental synchrony from per capita growth rates using obtainable abundance data even with realistic sampling noise, without the need to sort parasites into developmental stages. Our approach enables variability in developmental schedules to be disentangled from even extreme variation in population dynamics, providing a comparative metric of developmental synchrony.

ecology↗

bioRxiv2023

Testing a non-destructive assay to track Plasmodium sporozoites in mosquitoes over time

BackgroundThe extrinsic incubation period (EIP), defined as the time it takes for malaria parasites in a mosquito to become infectious to a vertebrate host, is one of the most influential parameters for malaria transmission but remains poorly understood. The EIP is usually estimated by quantifying salivary gland sporozoites in subsets of mosquitoes, which requires terminal sampling. However, assays that allow repeated sampling of individual mosquitoes over time could provide better resolution of the EIP. MethodsWe tested a non-destructive assay to quantify sporozoites of two rodent malaria species, Plasmodium chabaudi and Plasmodium berghei, expelled throughout 24hr windows, from sugar-feeding substrates using quantitative PCR. ResultsThe assay can quantify sporozoites from sugar-feeding substrates, but the prevalence of parasite positive substrates is low. Multiple methods to increase the detection of expelled parasites (running additional technical replicates; using groups rather than individual mosquitoes) did not increase the detection rate, suggesting that expulsion of sporozoites is variable and infrequent. ConclusionsWe reveal successful detection of expelled sporozoites from sugar-feeding substrates. However, investigations of the biological causes underlying the low detection rate of sporozoites (e.g. mosquito feeding behaviour, frequency of sporozoite expulsion, or sporozoite clumping) are needed to maximise the utility of using non-destructive assays to quantify sporozoite dynamics. Increasing detection rates will facilitate the detailed investigation on infection dynamics within mosquitoes, which is necessary to explain Plasmodiums highly variable EIP and improve understanding of malaria transmission dynamics.

microbiology↗

bioRxiv2023

Consequences of daily rhythm disruption on host-parasite malaria infection dynamics

Undertaking certain activities at the time of day that maximises fitness is assumed to explain the evolution of circadian clocks. Organisms often use daily environmental cues such as light and food availability to set the timing of their clocks. These cues may be the environmental rhythms that ultimately determine fitness, act as proxies for the timing of less tractable ultimate drivers, or are used simply to maintain internal synchrony. While many pathogens/parasites undertake rhythmic activities, both the proximate and ultimate drivers of their rhythms are poorly understood. Explaining the roles of rhythms in infections offers avenues for novel interventions to interfere with parasite fitness and reduce the severity and spread of disease. Here, we perturb several rhythms in the hosts of malaria parasites to investigate why parasites align their rhythmic replication to the hosts feeding-fasting rhythm. We manipulated host rhythms governed by light, food, or both, and assessed the fitness implications for parasites, and the consequences for hosts, to test which host rhythms represent ultimate drivers of the parasites rhythm. We found that alignment with the hosts light-driven rhythms did not affect parasite fitness metrics. In contrast, aligning with the timing of feeding-fasting rhythms may be beneficial for the parasite, but only when the host possess a functional canonical circadian clock. Because parasites in clock-disrupted hosts align with the hosts feeding-fasting rhythms and yet derive no apparent benefit, our results suggest cue(s) from host food act as a proxy rather than being a key selective driver of the parasites rhythm. Alternatively, parasite rhythmicity may only be beneficial because it promotes synchrony between parasite cells and/or allows parasites to align to the biting rhythms of vectors. Our results also suggest that interventions can disrupt parasite rhythms by targeting the proxies or the selective factors driving them without impacting host health.

evolutionary biology↗

bioRxiv2023

Virulence is associated with daily rhythms in the within-host replication of the malaria parasite Plasmodium chabaudi

Asexually replicating stages of most malaria (Plasmodium spp.) parasite species replicate synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasites rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes of Plasmodium, yet this variation is poorly understood. Theory predicts that virulence and IDC synchrony are negatively correlated and we tested this hypothesis using two closely related genotypes of the rodent malaria model Plasmodium chabaudi that differ markedly in virulence. We also test the predictions that in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness loss, and so, hosts benefit less from misalignment of the virulent genotype. Our predictions are partially supported; the virulent parasite genotype was less synchronous in some circumstances and recovered faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule and host rhythms, and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.

evolutionary biology↗

bioRxiv2023

The impact of innate immunity on malaria parasite infection dynamics

1Decades of research have investigated the molecular and cellular mechanisms that control the immune response to malaria. Yet, many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to probe for consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate and statistically analyse infection dynamics in immune deficient or augmented mice to identify and quantify consensus and identify sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohens h) for the difference in parasite burden between treatment and control groups ranging from 0.1498 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 6-12% on average at the peak of infection. Second, we reveal that variation across studies using P. chabaudi or P. yoelii is best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that for P. berghei the impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effects sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these explanations is necessary to translate understanding from model systems to human malaria infections, manage immunopathology, and facilitate realism in mathematical models.

evolutionary biology↗

bioRxiv2020

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

Rapid asexual replication of blood stage malaria parasites is responsible for the severity of disease symptoms and fuels the production of transmission forms. That malaria parasite species coordinate their cycles of asexual replication with daily rhythms of their host was discovered in the Hippocratic era, but how and why this occurs is enigmatic. Here, we demonstrate that the Plasmodium chabaudis schedule for asexual replication can be orchestrated by a isoleucine, metabolite provided to the parasite in periodic manner due to the hosts rhythmic intake of food. First, we identify nutrients with daily rhythms in the blood that match the timing of rhythms in both host feeding and the developmental schedule of asexually replicating parasites. We hypothesise that if parasites set their own developmental schedule, they should use a time-of-day cue that is a factor they cannot generate endogenously at any time-of-day, or scavenge in a round-the-clock manner. Our large-scale metabolomics experiment reveals that only one metabolite - the amino acid isoleucine - fits these criteria. Second, further experiments reveal that parasites alter the developmental schedule of asexual stages in response to isoleucine provision and withdrawal in the manner consistent with it acting as a time-cue. Specifically, parasites respond to isoleucine loss by slowing development. This is a parasite strategy rather than the consequences of an imposed constraint, because unlike when parasites are deprived of other essential nutrients, they suffer no apparent costs in the absence of isoleucine. Overall, our data suggest parasites can use the daily rhythmicity of blood-isoleucine concentration to synchronise asexual development with the availability of isoleucine, and potentially other resources, that arrive in the blood in a periodic manner due to the hosts daily feeding-fasting cycle. Identifying both how and why parasites keep time opens avenues for interventions; interfering with the parasites time-keeping mechanism may stall replication, increasing the efficacy of drugs and immune responses, and could also prevent parasites from entering dormancy to tolerate drugs.

microbiology↗

bioRxiv2019

Disruption of the coordination between host circadian rhythms and malaria parasite development alters the duration of the intraerythrocytic cycle

Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 hours (depending on the species), suggesting a circadian basis to the asexual cell cycle, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches using rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit 24 h \"circadian\" periodicity in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 9% of Plasmodium falciparum genes show circadian transcription under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a circadian transcription profile and disrupting it in rodent malaria parasites shortens the IDC by 2-3 hours; (v) Multiple processes including DNA replication and the ubiquitin and proteasome pathways are affected by loss of coordination with host rhythms and by disruption of SR10. Our results show that malaria parasites are at least partly responsible for scheduling their IDCs explaining the fitness benefits of coordination with host rhythms.

genomics↗

bioRxiv2019

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 behaviours and physiologies, including immune responses. Parasites also exhibit rhythms in within-host activities; the timing of host feeding sets the timing of the within-host replication of malaria parasites. Why host feeding matters to parasites and how coordination with feeding is achieved are unknown. Determining whether parasites coordinate with clock-driven food-related rhythms of their hosts matters because rhythmic replication underpins disease symptoms and fuels transmission.\n\nWe find that parasite rhythms became coordinated with the time of day that hosts feed in both wild type and clock-mutant mice, whereas parasite rhythmicity was lost in clock-mutant mice that fed continuously. These patterns occurred regardless of whether infections were initiated with synchronous or with desynchronised parasites.\n\nMalaria parasite rhythms are not driven by canonical clock-controlled host rhythms. Instead, we propose parasites coordinate with a temporally-restricted nutrient that becomes available through host digestion or are influenced by a separate clock-independent host process that directly responds to feeding. Thus, interventions could disrupt parasite rhythms to reduce their fitness, without interference by host clock-controlled-homeostasis.

ecology↗

bioRxiv2019

Host circadian rhythms are disrupted during malaria infection in parasite genotype-specific manners

Infection can dramatically alter behavioural and physiological traits as hosts become sick and subsequently return to health. Such \"sickness behaviours\" include disrupted circadian rhythms in both locomotor activity and body temperature. Host sickness behaviours vary in pathogen species-specific manners but the influence of pathogen intraspecific variation is rarely studied. We examine how infection with the murine malaria parasite, Plasmodium chabaudi, shapes sickness in terms of parasite genotype-specific effects on host circadian rhythms. We reveal that circadian rhythms in host locomotor activity patterns and body temperature become differentially disrupted and in parasite genotype-specific manners. Locomotor activity and body temperature in combination provide more sensitive measures of health than commonly used virulence metrics for malaria (e.g. anaemia). Moreover, patterns of host disruption cannot be explained simply by variation in replication rate across parasite genotypes or the severity of anaemia each parasite genotype causes. It is well known that disruption to circadian rhythms is associated with non-infectious diseases, including cancer, type 2 diabetes, and obesity. Our results reveal that disruption of host circadian rhythms is a genetically variable virulence trait of pathogens with implications for host health and disease tolerance.

ecology↗

bioRxiv2018

Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes

That periodicity in the biting activity of mosquito vectors explains why malaria parasites have evolved rhythms in cycles of asexual replication in the hosts blood was proposed almost 50 years ago. Yet, tests of this hypothesis have proved inconclusive. Using the rodent malaria Plasmodium chabaudi, we examine rhythms in the density and infectivity of transmission forms (gametocytes) in the hosts blood, parasite development inside mosquitoes, and onwards transmission.Moreover, we control for the confounding effects of rhythms in mosquito susceptibility. We reveal that at night, gametocytes are twice as infective to mosquitoes, despite being less numerous in the blood. This enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens by almost four-fold when mosquitoes feed during their day. Thus, daytime blood-feeding (e.g. driven by the use of bed nets) may render gametocytes less infective, but this is compensated for by the greater susceptibility of mosquitoes.

microbiology↗

bioRxiv2017

Timing of host feeding drives rhythms in parasite replication

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 hosts 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 hosts 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.\n\nAuthor 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 hosts 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.

microbiology↗