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Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability.

ABSTRACT: The trade-off between survival and reproduction is fundamental in the life history of all sexually reproducing organisms. This includes malaria parasites, which rely on asexually replicating stages for within-host survival and on sexually reproducing stages (gametocytes) for between-host transmission. The proportion of asexual stages that form gametocytes (reproductive effort) varies during infections-i.e. is phenotypically plastic-in response to changes in a number of within-host factors, including anaemia. However, how the density and age structure of red blood cell (RBC) resources shape plasticity in reproductive effort and impacts upon parasite fitness is controversial. Here, we examine how and why the rodent malaria parasite Plasmodium chabaudi alters its reproductive effort in response to experimental perturbations of the density and age structure of RBCs. We show that all four of the genotypes studied increase reproductive effort when the proportion of RBCs that are immature is elevated during host anaemia, and that the responses of the genotypes differ. We propose that anaemia (counterintuitively) generates a resource-rich environment in which parasites can afford to allocate more energy to reproduction (i.e. transmission) and that anaemia also exposes genetic variation to selection. From an applied perspective, adaptive plasticity in parasite reproductive effort could explain the maintenance of genetic variation for virulence and why anaemia is often observed as a risk factor for transmission in human infections.

SUBMITTER: Birget PLG

PROVIDER: S-EPMC5563815 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability.

Birget Philip L G PLG Repton Charlotte C O'Donnell Aidan J AJ Schneider Petra P Reece Sarah E SE

Proceedings. Biological sciences 20170801 1860

The trade-off between survival and reproduction is fundamental in the life history of all sexually reproducing organisms. This includes malaria parasites, which rely on asexually replicating stages for within-host survival and on sexually reproducing stages (gametocytes) for between-host transmission. The proportion of asexual stages that form gametocytes (reproductive effort) varies during infections-i.e. is phenotypically plastic-in response to changes in a number of within-host factors, inclu ...[more]

PMID: 28768894

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Project description:Investment in the production of transmissible stages (gametocytes) and their sex ratio are malaria parasite traits that underpin mosquito infectivity and are therefore central to epidemiology. Malaria parasites adjust their levels of investment into gametocytes and sex ratio in response to changes in the in-host environment (including red blood cell resource availability, host immune responses, competition from con-specific genotypes in mixed infections, and drug treatment). This plasticity appears to be adaptive (strategic) because parasites prioritize investment (in sexual versus asexual stages and male versus female stages) in manners predicted to maximize fitness. However, the information, or 'cues' that parasites use to detect environmental changes and make appropriate decisions about investment into gametocytes and their sex ratio are unknown.Single genotype Plasmodium chabaudi infections were exposed to 'cue' treatments consisting of intact or lysed uninfected red blood cells, lysed parasitized RBCs of the same clone or an unrelated clone, and an unmanipulated control. Infection dynamics (proportion of reticulocytes, red blood cell and asexual stage parasite densities) were monitored, and changes in gametocyte investment and sex ratio in response to cue treatments, applied either pre- or post-peak of infection were examined.A significant reduction in gametocyte density was observed in response to the presence of lysed parasite material and a borderline significant increase in sex ratio (proportion of male gametocytes) upon exposure to lysed red blood cells (both uninfected and infected) was observed. Furthermore, the changes in gametocyte density and sex ratio in response to these cues depend on the age of infection. Demonstrating that variation in gametocyte investment and sex ratio observed during infections are a result of parasite strategies (rather than the footprint of host physiology), provides a foundation to investigate the fitness consequences of plasticity and explore whether drugs could be developed to trick parasites into making suboptimal decisions.

Project description:Background and objectivesPhenotypic plasticity enables organisms to maximize fitness by matching trait values to different environments. Such adaptive phenotypic plasticity is exhibited by parasites, which experience frequent environmental changes during their life cycle, between individual hosts and also in within-host conditions experienced during infections. Life history theory predicts that the evolution of adaptive phenotypic plasticity is limited by costs and constraints, but tests of these concepts are scarce.MethodologyHere, we induce phenotypic plasticity in malaria parasites to test whether mounting a plastic response to an environmental perturbation constrains subsequent plastic responses to further environmental change. Specifically, we perturb red blood cell resource availability to induce Plasmodium chabaudi to alter the trait values of several phenotypes underpinning within-host replication and between-host transmission. We then transfer parasites to unperturbed hosts to examine whether constraints govern the parasites' ability to alter these phenotypes in response to their new in-host environment.ResultsParasites alter trait values in response to the within-host environment they are exposed to. We do not detect negative consequences, for within-host replication or between-host transmission, of previously mounting a plastic response to a perturbed within-host environment.Conclusions and implicationsWe suggest that malaria parasites are highly plastic and adapted to adjusting their phenotypes in response to the frequent changes in the within-host conditions they experience during infections. Our findings support the growing body of evidence that medical interventions, such as anti-parasite drugs, induce plastic responses that are adaptive and can facilitate the survival and potentially, drug resistance of parasites.Lay summaryMalaria parasites have evolved flexible strategies to cope with the changing conditions they experience during infections. We show that using such flexible strategies does not impact upon the parasites' ability to grow (resulting in disease symptoms) or transmit (spreading the disease).

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Project description:The availability of high quality resources is an important factor driving community structure and reproductive mode of animals. Parthenogenetic reproduction prevails when resources are available in excess, whereas sexuality correlates with resource shortage. We investigated the effect of resource availability on the community structure of oribatid mites in a laboratory experiment. Availability of food resources was increased by addition of glucose to leaf litter and reduced by leaching of nutrients from leaf litter. Experimental systems were incubated at three different temperatures to establish different regimes of resource exploitation. Community structure of oribatids and numbers of eggs per female were measured over a period of ten months. We expected the density of oribatid mites to decline in the reduced litter quality treatment but to increase in the glucose treatment. Both effects were assumed to be more pronounced at higher temperatures. We hypothesized sexual species to be less affected than parthenogenetic species by reduced resource quality due to higher genetic diversity allowing more efficient exploitation of limited resources, but to be outnumbered by parthenogenetic species in case of resource addition due to faster reproduction. In contrast to our hypotheses, both sexual and parthenogenetic oribatid mite species responded similarly with their densities declining uniformly during incubation. The parthenogenetic Brachychthoniidae and Tectocepheus dominated early in the experiment but were replaced later by parthenogenetic Desmonomata and Rhysotritia. In parthenogenetic species the number of eggs per female increased during the experiment while the number of eggs in sexual females remained constant or decreased slightly; in general, egg numbers were higher in sexual than in parthenogenetic species. The results indicate that for sustaining oribatid mite populations other resources than litter and associated saprotrophic microorganisms are needed. They also indicate that there are two groups of parthenogenetically reproducing species: exploiters of easily available resources and consumers of leaf litter associated resources.

Project description:In the malaria parasite Plasmodium falciparum, synthesis of isoprenoids from glycolytic intermediates is essential for survival. The antimalarial fosmidomycin (FSM) inhibits isoprenoid synthesis. In P. falciparum, we identified a loss-of-function mutation in HAD2 (P. falciparum 3D7_1226300 [PF3D7_1226300]) as necessary for FSM resistance. Enzymatic characterization revealed that HAD2, a member of the haloacid dehalogenase-like hydrolase (HAD) superfamily, is a phosphatase. Harnessing a growth defect in resistant parasites, we selected for suppression of HAD2-mediated FSM resistance and uncovered hypomorphic suppressor mutations in the locus encoding the glycolytic enzyme phosphofructokinase 9 (PFK9). Metabolic profiling demonstrated that FSM resistance is achieved via increased steady-state levels of methylerythritol phosphate (MEP) pathway and glycolytic intermediates and confirmed reduced PFK9 function in the suppressed strains. We identified HAD2 as a novel regulator of malaria parasite metabolism and drug sensitivity and uncovered PFK9 as a novel site of genetic metabolic plasticity in the parasite. Our report informs the biological functions of an evolutionarily conserved family of metabolic regulators and reveals a previously undescribed strategy by which malaria parasites adapt to cellular metabolic dysregulation.IMPORTANCE Unique and essential aspects of parasite metabolism are excellent targets for development of new antimalarials. An improved understanding of parasite metabolism and drug resistance mechanisms is urgently needed. The antibiotic fosmidomycin targets the synthesis of essential isoprenoid compounds from glucose and is a candidate for antimalarial development. Our report identifies a novel mechanism of drug resistance and further describes a family of metabolic regulators in the parasite. Using a novel forward genetic approach, we also uncovered mutations that suppress drug resistance in the glycolytic enzyme PFK9. Thus, we identify an unexpected genetic mechanism of adaptation to metabolic insult that influences parasite fitness and tolerance of antimalarials.

Dataset Information

Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability.

Publications

Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability.

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