Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

Nobuyuki Kobayashi,Richard Culleton,Julie-Anne Tangena,Augustin Zoungrana,Nick Colegrave,Hussein M Abkallo,Megumi Inoue,Jianxia Tang

doi:10.1371/journal.ppat.1004628

Nobuyuki Kobayashi, Richard Culleton + Show 6 more

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https://doi.org/10.1371/journal.ppat.1004628

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Abstract

In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

Highlights

IntroductionA series of experiments performed exclusively with strains of the rodent malaria parasite Plasmodium chabaudi, suggested that faster growing strains gained a competitive advantage over slower growing strains [7], in that they often dominated mixed strain infections in terms of proportional numbers of parasites, and sometimes competitively excluded the slower growing strain at some point during the infection
Malaria is caused by a diverse group of parasites composed of at least six species of the genus Plasmodium
Malaria infections are very often composed of multiple strains of malaria parasites

Summary

Introduction

A series of experiments performed exclusively with strains of the rodent malaria parasite Plasmodium chabaudi, suggested that faster growing strains gained a competitive advantage over slower growing strains [7], in that they often dominated mixed strain infections in terms of proportional numbers of parasites, and sometimes competitively excluded the slower growing strain at some point during the infection. This has been interpreted as suggesting that withinhost competition could lead to the selection of virulence within a parasite population

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