Mikaberidze Alexey, Paveley Neil, Bonhoeffer Sebastian, van den Bosch Frank
First author: Plant Pathology Group, Institute of Integrative Biology, ETH Zurich, LFW, Zurich, CH-8092, Switzerland; second author: ADAS, Duggleby YO17 8BP, United Kingdom; third author: Theoretical Biology, Institute of Integrative Biology, ETH Zurich, CHN, Zurich, CH-8092; and fourth author: Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom.
Phytopathology. 2017 May;107(5):545-560. doi: 10.1094/PHYTO-08-16-0297-R. Epub 2017 Mar 28.
Resistance to antimicrobial drugs allows pathogens to survive drug treatment. The time taken for a new resistant mutant to reach a population size that is unlikely to die out by chance is called "emergence time." Prolonging emergence time would delay loss of control. We investigate the effect of fungicide dose on the emergence time in fungal plant pathogens. A population dynamical model is combined with dose-response data for Zymoseptoria tritici, an important wheat pathogen. Fungicides suppress sensitive pathogen population. This has two effects. First, the rate of appearance of resistant mutants is reduced, hence the emergence takes longer. Second, more healthy host tissue becomes available for resistant mutants, increasing their chances to invade and accelerates emergence. In theory, the two competing effects may lead to a non-monotonic dependence of the emergence time on fungicide dose that exhibits a minimum. But according to field data, fungicides are unable to reduce the fungicide-sensitive population strongly enough even at high doses. Hence, for full resistance over realistic ranges of pathogen's life history and fungicide dose-response parameters, emergence time decreases monotonically with increasing dose. For partial resistance, there can be cases within a limited parameter range, when emergence decelerates at higher doses.
对抗菌药物产生耐药性会使病原体在药物治疗中存活下来。新的耐药突变体达到一个不太可能因偶然因素灭绝的种群规模所需的时间被称为“出现时间”。延长出现时间会延迟失控情况的发生。我们研究了杀菌剂剂量对真菌植物病原体出现时间的影响。将一个种群动力学模型与重要小麦病原体小麦黄斑叶枯病菌（Zymoseptoria tritici）的剂量反应数据相结合。杀菌剂会抑制敏感病原体种群。这有两个影响。首先，耐药突变体的出现速率降低，因此出现时间变长。其次，更多健康的宿主组织可供耐药突变体利用，增加了它们入侵的机会并加速了出现。理论上，这两种相互竞争的影响可能导致出现时间对杀菌剂剂量呈现非单调依赖关系，并出现一个最小值。但根据田间数据，即使在高剂量下，杀菌剂也无法充分强烈地减少对杀菌剂敏感的种群。因此，对于在病原体现实的生活史范围和杀菌剂剂量反应参数范围内的完全耐药情况，出现时间会随着剂量增加而单调减少。对于部分耐药情况，在有限的参数范围内可能存在这样的情况，即出现时间在较高剂量时会减速。
