Evolutionary emergence of infectious diseases in heterogeneous host populations.
Evolutionary emergence of infectious diseases in heterogeneous host populations.
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DOI：
10.1371/journal.pbio.2006738
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发表时间：
2018-09
期刊：
影响因子：
9.8
通讯作者：
Gandon S
中科院分区：
文献类型：
--
作者：
Chabas H;Lion S;Nicot A;Meaden S;van Houte S;Moineau S;Wahl LM;Westra ER;Gandon S
病原体的出现和重新出现仍然是一个重大的公共卫生问题。不幸的是，众所周知，病原体将在何时何地（重新）出现是很难预测的，因为这些事件的不稳定性因流行病早期病原体演变的随机性而得到加强。例如，允许病原体逃避宿主抗性的突变可能会促进病原体的传播并促进出现。然而，由于目前的理论框架缺乏生态现实主义，并且难以通过实验验证其预测，因此控制这种进化出现的生态因素仍然难以捉摸。在这里，我们开发了一个理论模型来探索宿主种群的异质性对病原体出现概率的影响，有或没有病原体进化。我们表明，进化出现和逃逸突变的病原体种群的传播更有可能发生时，宿主种群包含一个中间比例的耐药主机。我们还表明，病原体出现的概率迅速下降的多样性，在主机人口的电阻。使用裂解性噬菌体感染其细菌宿主的实验测试证实了这些理论预测，所述细菌宿主含有重复的规则间隔短回文重复序列和CRISPR相关（CRISPR-Cas）免疫防御。这些结果表明，跨物种的溢出和新出现的传染病的管理的有效策略。流行病爆发的概率在很大程度上取决于病原体获得新的适应性突变和诱导进化出现的能力。因此，预测病原体的出现需要很好地了解疫情爆发时流行病学和进化之间的相互作用。在这里，我们提供了一个全面的理论框架来分析宿主种群异质性对病原体进化出现概率的影响。我们使用这个模型来预测的影响，易感主机的分数，病原体的接种量，和多样性的主机上的病原体出现的阻力。我们使用裂解性噬菌体和CRISPR抗性细菌的实验支持了我们的理论预测，并证明操纵宿主群体中抗性等位基因的多样性可能是限制新病原体出现的有效方法。
The emergence and re-emergence of pathogens remains a major public health concern. Unfortunately, when and where pathogens will (re-)emerge is notoriously difficult to predict, as the erratic nature of those events is reinforced by the stochastic nature of pathogen evolution during the early phase of an epidemic. For instance, mutations allowing pathogens to escape host resistance may boost pathogen spread and promote emergence. Yet, the ecological factors that govern such evolutionary emergence remain elusive because of the lack of ecological realism of current theoretical frameworks and the difficulty of experimentally testing their predictions. Here, we develop a theoretical model to explore the effects of the heterogeneity of the host population on the probability of pathogen emergence, with or without pathogen evolution. We show that evolutionary emergence and the spread of escape mutations in the pathogen population is more likely to occur when the host population contains an intermediate proportion of resistant hosts. We also show that the probability of pathogen emergence rapidly declines with the diversity of resistance in the host population. Experimental tests using lytic bacteriophages infecting their bacterial hosts containing Clustered Regularly Interspaced Short Palindromic Repeat and CRISPR-associated (CRISPR-Cas) immune defenses confirm these theoretical predictions. These results suggest effective strategies for cross-species spillover and for the management of emerging infectious diseases. The probability that an epidemic will break out is highly dependent on the ability of the pathogen to acquire new adaptive mutations and to induce evolutionary emergence. Forecasting pathogen emergence thus requires a good understanding of the interplay between the epidemiology and evolution taking place at the onset of an outbreak. Here, we provide a comprehensive theoretical framework to analyze the impact of host population heterogeneity on the probability of pathogen evolutionary emergence. We use this model to predict the impact of the fraction of susceptible hosts, the inoculum size of the pathogen, and the diversity of host resistance on pathogen emergence. Our experiments using lytic bacteriophages and CRISPR-resistant bacteria support our theoretical predictions and demonstrate that manipulating the diversity of resistance alleles in a host population may be an effective way to limit the emergence of new pathogens.
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影响因子：
4.3
作者：
Day T;Read AF
通讯作者：
Read AF
影响因子：
5.6
作者：
REX Consortium
通讯作者：
REX Consortium
DOI：
10.1126/science.aaa4339
发表时间：
2015-03-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heesterbeek H;Anderson RM;Andreasen V;Bansal S;De Angelis D;Dye C;Eames KT;Edmunds WJ;Frost SD;Funk S;Hollingsworth TD;House T;Isham V;Klepac P;Lessler J;Lloyd-Smith JO;Metcalf CJ;Mollison D;Pellis L;Pulliam JR;Roberts MG;Viboud C;Isaac Newton Institute IDD Collaboration
通讯作者：
Isaac Newton Institute IDD Collaboration
影响因子：
3.2
作者：
Deveau, Helene;Barrangou, Rodolphe;Moineau, Sylvain
通讯作者：
Moineau, Sylvain
影响因子：
3.9
作者：
Alexander, H. K.;Day, T.
通讯作者：
Day, T.