Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi.
Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi.
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DOI：
10.1098/rspb.2012.1792
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发表时间：
2012-11-22
期刊：
影响因子：
--
通讯作者：
Reece SE
中科院分区：
文献类型：
--
作者：
Schneider P;Bell AS;Sim DG;O'Donnell AJ;Blanford S;Paaijmans KP;Read AF;Reece SE
在这里，我们测试了一种假设，即致病性疟疾寄生虫比致病性较弱的寄生虫更不容易受到药物治疗的影响。如果是真的，药物治疗可能会促进毒性更强的寄生虫(这里的定义是对宿主造成更大伤害的寄生虫)的进化。通过在亚细胞水平上与药物分子相互作用来保护寄生虫的耐药性机制是众所周知的。然而，与毒力相关的寄生虫表型也可能有助于寄生虫在药物存在的情况下存活。例如，如果药物治疗不能消除寄生虫，快速复制的寄生虫可能在宿主体内恢复得更好。我们量化了药物治疗对啮齿动物疟疾寄生虫在宿主内存活和宿主间传播的影响，这些寄生虫的毒力不同，以前从未接触过药物。在我们的所有治疗方案中，在单一和混合基因感染中，毒力强的寄生虫对我们测试的两种抗疟疾药物乙胺嘧啶和青蒿素不太敏感。当接触乙丙胺时，毒力强的寄生虫也实现了不成比例的更大传播。总体而言，我们的数据表明，药物治疗可以选择毒力更强的寄生虫。针对传播阶段的药物(如青蒿素)可能会使药物治疗感染中毒力的进化优势最小化。
Here, we test the hypothesis that virulent malaria parasites are less susceptible to drug treatment than less virulent parasites. If true, drug treatment might promote the evolution of more virulent parasites (defined here as those doing more harm to hosts). Drug-resistance mechanisms that protect parasites through interactions with drug molecules at the sub-cellular level are well known. However, parasite phenotypes associated with virulence might also help parasites survive in the presence of drugs. For example, rapidly replicating parasites might be better able to recover in the host if drug treatment fails to eliminate parasites. We quantified the effects of drug treatment on the in-host survival and between-host transmission of rodent malaria (Plasmodium chabaudi) parasites which differed in virulence and had never been previously exposed to drugs. In all our treatment regimens and in single- and mixed-genotype infections, virulent parasites were less sensitive to pyrimethamine and artemisinin, the two antimalarial drugs we tested. Virulent parasites also achieved disproportionately greater transmission when exposed to pyrimethamine. Overall, our data suggest that drug treatment can select for more virulent parasites. Drugs targeting transmission stages (such as artemisinin) may minimize the evolutionary advantage of virulence in drug-treated infections.
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DOI：
10.1073/pnas.0500078102
发表时间：
2005-05-24
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
2.4
作者：
Lynch, Penelope A.;Grimm, Uwe;Read, Andrew F.
通讯作者：
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