Rapid Parallel Evolution of Azole Fungicide Resistance in Australian Populations of the Wheat Pathogen Zymoseptoria tritici
Rapid Parallel Evolution of Azole Fungicide Resistance in Australian Populations of the Wheat Pathogen Zymoseptoria tritici
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DOI：
10.1128/aem.01908-18
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发表时间：
2019-02-01
影响因子：
4.4
通讯作者：
Milgate, Andrew
中科院分区：
文献类型：
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作者：
McDonald, Megan C.;Renkin, Melanie;Milgate, Andrew
小麦发酵斑孢菌(Zymoseptoria tritici)是一种全球分布的真菌病原体，可引起小麦上的小麦壳针孢斑病。尝试通过部署抗性小麦品种和使用杀菌剂来控制该病害。然而，在小麦小麦群体中普遍观察到杀菌剂抗性，并且需要持续监测以检测杀菌剂效力的下降。我们最近报道了澳大利亚的唑类抗性分离株；然而，尚不清楚耐药性是通过基因流动带入非洲大陆还是单独出现。为了解决这个问题，我们对澳大利亚 5 个地点的 43 个分离株进行了唑类敏感性筛查，并对来自 7 个地点的 58 个分离株进行了全基因组测序，以确定耐药性的遗传基础。人群基因组分析显示，在唑类药物开始使用后恢复的澳大利亚人群与唑类药物开始使用前恢复的澳大利亚人群以及不同大陆的人群之间存在极强的差异。澳大利亚和其他大陆之间最近明显缺乏基因流动，这表明唑类杀菌剂耐药性已经从头进化出来，并随后在塔斯马尼亚境内传播。尽管分离株在全基因组水平上是不同的，但我们在 CYP51 位点观察到非同义取代组合，与世界其他地方观察到的相同。我们观察到九个先前报告的非同义突变以及携带先前报告的 L50S、S188N、A379G、I381V、Y459DEL、G460DEL 和 N513K 取代组合的分离株。对暴露于戊唑醇和氧环唑杀菌剂的部分分离株进行的 50% 有效浓度测定显示出高水平的唑类抗性。与欧洲主要单倍型相匹配的复杂 CYP51 单倍型的快速、平行进化证明了病原真菌中从头出现抗性的巨大潜力。重要性 杀菌剂对于控制农业疾病至关重要，因为许多作物对病原体高度敏感。然而，许多病原体迅速进化出对杀菌剂的抗药性。大量研究已经描述了赋予耐药性的特定突变，并且通常仅根据靶基因的测序数据来推断耐药性的起源。在这里，我们展示了澳大利亚塔斯马尼亚的小麦病原体小麦发酵斑孢菌基因分离群体对普遍使用的唑类杀菌剂的抗药性从头获得。我们通过对全球代表性人群的基因组规模分析来确认平行进化的证据。最近有据可查地将唑类引入澳大利亚农业实践后，复杂抗性单倍型的出现表明了农业生态系统中化学抗性的演变有多快。
Zymoseptoria tritici is a globally distributed fungal pathogen which causes Septoria tritici blotch on wheat. Management of the disease is attempted through the deployment of resistant wheat cultivars and the application of fungicides. However, fungicide resistance is commonly observed in Z. tritici populations, and continuous monitoring is required to detect breakdowns in fungicide efficacy. We recently reported azole-resistant isolates in Australia; however, it remained unknown whether resistance was brought into the continent through gene flow or whether resistance emerged independently. To address this question, we screened 43 isolates across five Australian locations for azole sensitivity and performed whole-genome sequencing on 58 isolates from seven locations to determine the genetic basis of resistance. Population genomic analyses showed extremely strong differentiation between the Australian population recovered after azoles began to be used and both Australian populations recovered before azoles began to be used and populations on different continents. The apparent absence of recent gene flow between Australia and other continents suggests that azole fungicide resistance has evolved de novo and subsequently spread within Tasmania. Despite the isolates being distinct at the whole-genome level, we observed combinations of nonsynonymous substitutions at the CYP51 locus identical to those observed elsewhere in the world. We observed nine previously reported nonsynonymous mutations as well as isolates that carried a combination of the previously reported L50S, S188N, A379G, I381V, Y459DEL, G460DEL, and N513K substitutions. Assays for the 50% effective concentration against a subset of isolates exposed to the tebuconazole and epoxiconazole fungicides showed high levels of azole resistance. The rapid, parallel evolution of a complex CYP51 haplotype that matches a dominant European haplotype demonstrates the enormous potential for de novo resistance emergence in pathogenic fungi.IMPORTANCE Fungicides are essential to control diseases in agriculture because many crops are highly susceptible to pathogens. However, many pathogens rapidly evolve resistance to fungicides. A large body of studies have described specific mutations conferring resistance and have often made inferences about the origins of resistance based on sequencing data from the target gene alone. Here, we show the de novo acquisition of resistance to the ubiquitously used azole fungicides in genetically isolated populations of the wheat pathogen Zymoseptoria tritici in Tasmania, Australia. We confirm evidence for parallel evolution through genome-scale analyses of representative worldwide populations. The emergence of complex resistance haplotypes following a well-documented recent introduction of azoles into Australian farming practices demonstrates how rapidly chemical resistance evolves in agricultural ecosystems.