Data from: Within-host competition in genetically diverse malaria infections: parasite virulence and competitive success.

Humans and animals often become coinfected with pathogen strains that differ in virulence. The ensuing interaction between these strains can, in theory, be a major determinant of the direction of selection on virulence genes in pathogen populations. Many mathematical analyses of this assume that virulent pathogen lineages have a competitive advantage within coinfected hosts and thus predict that pathogens will evolve to become more virulent where genetically diverse infections are common. Although the implications of these studies are relevant to both fundamental biology and medical science, direct empirical tests for relationships between virulence and competitive ability are lacking. Here we use newly developed strain-specific real-time quantitative polymerase chain reaction protocols to determine the pairwise competitiveness of genetically divergent Plasmodium chabaudi clones that represent a wide range of innate virulences in their rodent host. We found that even against their background of widely varying genotypic and antigenic properties, virulent clones had a competitive advantage in the acute phase of mixed infections. The more virulent a clone was relative to its competitor, the less it suffered from competition. This result confirms our earlier work with parasite lines derived from a single clonal lineage by serial passage and supports the virulence-competitive ability assumption of many theoretical models. To the extent that our rodent model captures the essence of the natural history of malaria parasites, public health interventions which reduce the incidence of mixed malaria infections should have beneficial consequences by reducing the selection for high virulence.人类与动物常同时感染毒力存在差异的病原体菌株。理论上，这些菌株间的相互作用可成为决定病原体种群中毒力基因选择方向的核心因素。诸多相关数学分析均假定，高毒力病原体谱系在共感染宿主内具备竞争优势，并据此预测：在基因多样型感染高发的环境中，病原体将向更高毒力的方向演化。尽管此类研究的结论对基础生物学与医学均具有重要参考价值，但目前仍缺乏针对毒力与竞争能力间关联的直接实证检验。本研究采用全新开发的菌株特异性实时定量聚合酶链反应（real-time quantitative polymerase chain reaction）实验方案，针对在啮齿动物宿主中展现出广泛天然毒力差异的基因分化型查氏疟原虫（Plasmodium chabaudi）克隆株，测定其两两间的竞争能力。研究发现，即便在基因型与抗原特性差异显著的背景下，高毒力克隆株在混合感染的急性期仍具备竞争优势。相较于其竞争株，克隆株的毒力越强，自身受到竞争抑制的程度就越低。这一结果不仅验证了我们此前通过连续传代获得的单克隆起源寄生虫株系的相关研究结论，同时也为诸多理论模型中“毒力与竞争能力正相关”的假设提供了支撑。若本研究所用的啮齿动物模型能够反映疟原虫自然感染的核心特征，那么通过降低混合疟疾感染发生率的公共卫生干预手段，将通过削弱针对高毒力菌株的选择压力而产生有益效果。