Abstract
Hosts are often infected with multiple strains of a single parasite species. Within-host competition between parasite strains can be intense and has implications for the evolution of traits that impact patient health, such as drug resistance and virulence. Yet the mechanistic basis of within-host competition is poorly understood. Here, we demonstrate that a parasite nutrient, para-aminobenzoic acid (pABA), mediates competition between a drug resistant and drug susceptible strain of the malaria parasite, Plasmodium chabaudi. We further show that increasing pABA supply to hosts infected with the resistant strain worsens disease and changes the relationship between parasite burden and pathology. Our experiments demonstrate that, even when there is profound top-down regulation (immunity), bottom-up regulation of pathogen populations can occur and that its importance may vary during an infection. The identification of resources that can be experimentally controlled opens up the opportunity to manipulate competitive interactions between parasites and hence their evolution.
Highlights
Hosts are often infected by multiple parasite ‘strains’—parasites of the same species that have a different genotype and, often, phenotype [1,2]
We show that the intensity of competition between these strains of P. chabaudi in the period before they are cleared by the immune system varies over a gradient of pABA supply and that resource availability changes the relationship between parasite burden and pathology
The temporal dynamics of infections were analysed using linear mixed effects (LME) models following [42,43,44], with day fitted as a factor to allow for nonlinearity in infection dynamics, individual mouse fitted as a random effect, a corAR1 autocorrelation structure fitted to correct for temporal autocorrelation and a variance structure that accounted for changes in residual variance in parasite density between days
Summary
Hosts are often infected by multiple parasite ‘strains’—parasites of the same species that have a different genotype and, often, phenotype [1,2]. We investigate the impact of pABA concentration on the intensity of competition between two genetically distinct strains of P. chabaudi, AJ and ASpyr. Competition between these strains is well characterized and asymmetrical: in mice inoculated with the two strains at the same time, AJ strongly suppresses ASpyr; ASpyr has little to no effect on AJ [4,5,36,37]. We show that the intensity of competition between these strains of P. chabaudi in the period before they are cleared by the immune system varies over a gradient of pABA supply and that resource availability changes the relationship between parasite burden and pathology
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