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

Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.
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DOI:
10.1371/journal.ppat.1004628
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发表时间:
2015-02
期刊:
影响因子:
6.7
通讯作者:
Culleton R
Culleton R
中科院分区:
医学1区
文献类型:
--
作者:
Abkallo HM;Tangena JA;Tang J;Kobayashi N;Inoue M;Zoungrana A;Colegrave N;Culleton R

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在传播强度高的流行地区,疟疾感染通常由多种遗传上不同的疟疾寄生虫菌株组成。据推测,这导致了宿主内竞争,其中寄生虫菌株争夺空间和营养等资源。这种竞争可能对宿主、寄生虫和病媒在疾病严重程度、病媒适应度以及寄生虫传播潜力和适应度方面产生影响。也有人认为,宿主内的竞争可能导致选择毒性更强的寄生虫。在这里,我们使用啮齿动物疟疾寄生虫约利疟原虫来评估混合菌株感染对疾病严重程度和寄生虫适应性的影响。在小鼠的单一感染或具有遗传不同菌株的混合菌株感染中,维持了三种具有显著不同生长速度(因此毒性)的等基因菌株。我们比较了混合菌株感染与单一感染的毒力(定义为对哺乳动物宿主的危害),并通过传播潜力评估竞争是否会影响寄生虫的适应性。我们发现混合感染与较高的疾病严重程度和较长的感染时间有关。在混合感染中,生长速度较慢的菌株通常负责竞争性排除生长速度较快的菌株,可能是通过宿主免疫介导的机制。重要的是,与之前对chabaudi疟原虫的研究相比,我们发现寄生虫毒力与蚊子传播潜力之间没有相关性,这表明寄主内竞争不会推动P. yoelii寄生虫毒力的进化。疟疾感染通常由多种疟疾寄生虫菌株组成。据认为,这些菌株可能会在宿主体内竞争空间和营养等资源。在这里,我们表明这种“宿主内竞争”对疟疾感染的毒力有影响,因此,就疾病严重程度而言,由多个菌株组成的感染比含有组成寄生虫的单一菌株感染更具毒力。由此,有人提出,由于这种竞争有利于那些生长速度更快的寄生虫,那么当宿主内竞争普遍存在时,这些寄生虫就会在自然界中被选择。然而,我们表明,情况并非如此,因为在哺乳动物宿主中生长速度较快的寄生虫并不比生长速度较慢的寄生虫更成功地传播给蚊子。这些结果表明,需要重新评估我们目前对宿主内竞争在疟疾寄生虫毒力选择中的作用的理解。
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. Malaria infections are very often composed of multiple strains of malaria parasites. It is thought that these strains may compete for resources such as space and nutrients within the host. Here we show that such “within-host competition” has repercussions for the virulence of the malaria infection, so that infections composed of multiple strains are more virulent in terms of disease severity, than single strain infections containing the constituent parasites. Following from this, it has been proposed that as such competition would favour those parasites with faster growth rates, then these parasites would be selected in nature when within-host competition is common. We show, however, that this is not necessarily the case, as parasites with faster growth rates in the mammalian host were no more successful at transmitting to mosquitoes than parasites with slower growth rates. These results show that a reassessment of our current understanding of the role of within-host competition in the selection of virulence in malaria parasites is required.
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