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首页> 外文期刊>Applied Microbiology >Aspergillus fumigatus Cross-Resistance between Clinical and Demethylase Inhibitor Azole Drugs
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Aspergillus fumigatus Cross-Resistance between Clinical and Demethylase Inhibitor Azole Drugs

机译：临床和去甲基酶抑制剂唑类唑类唑类唑类唑类药物

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Drug resistance poses a serious threat to human health and agricultural production. Azole drugs are the largest group of 14-α sterol demethylation inhibitor fungicides that are used both in agriculture and in clinical practice. As plant-pathogenic molds share their natural environment with fungi that cause opportunistic infections in humans, both are exposed to a strong and persistent pressure of demethylase inhibitor (DMI) fungicides, including imidazole and triazole drugs. As a result, a loss of efficacy has occurred for this drug class in several species. In the clinical setting, Aspergillus fumigatus azole resistance is a growing public health problem, and finding the source of this resistance has gained much attention. It is urgent to determine if there is a direct link between the agricultural use of azole compounds and the different A. fumigatus resistance mechanisms described for clinical triazoles. In this study, we performed A. fumigatus susceptibility testing against clinical triazoles and crop protection DMIs using a collection of azole-susceptible and -resistant strains which harbor most of the described azole resistance mechanisms. Various DMI susceptibility profiles have been found in the different A. fumigatus population groups based on their azole resistance mechanism and previous whole-genome sequencing (WGS) analysis, which suggests that the different resistance mechanisms have different origins and are specifically associated with the local use of a particular DMI.IMPORTANCE Due to the worldwide emergence of A. fumigatus azole resistance, this opportunistic pathogen poses a serious health threat, and therefore, it has been included in the watch list in the CDC publication Antibiotic Resistance Threats in the United States, 2019 (CDC, 2019). Azoles play a critical role in the control and management of fungal diseases, not only in the clinical setting but also in agriculture. Thus, azole resistance leads to a limited therapeutic arsenal which reduces the treatment options for aspergillosis patients, increasing their mortality risk. Evidence is needed to understand whether A. fumigatus azole resistance is emerging from an agricultural source due to the extended use of demethylase inhibitors as fungicides or whether it is coming from somewhere else, such as the clinical setting. If the environmental route is demonstrated, the current use and management of azole antifungal compounds might be forced to change in the coming years.
机译：耐药构成对人类健康和农业生产的严重威胁。唑类药物是最大的14-α甾醇去甲基化抑制剂杀菌剂，其在农业和临床实践中使用。由于植物 - 病原模具与对人类机会性感染的真菌共享他们的自然环境，因此两者都暴露于脱甲酶抑制剂（DMI）杀菌剂的强大和持续的压力，包括咪唑和三唑类药物。结果，在几种药物课程中发生了疗效的损失。在临床环境中，Aspergillus fumigatus唑抗性是一种不断增长的公共卫生问题，并发现这种抵抗力的来源越来越大。迫切需要确定唑类化合物的农业使用与临床三唑的不同A.富泻抗性机制之间是否存在直接联系。在这项研究中，我们使用一系列唑易受和 - 抗生素菌株对临床三唑和作物保护DMI进行了Fumigatus易感性测试，这些唑易溶性和抗性菌株。在不同的A. Fumigatus群体基于唑抗抗性机制和先前的全基因组测序（WGS）分析中，已经发现了各种DMI易感性曲线，这表明不同的电阻机制具有不同的起源，并且与局部使用有关特定的DMI.Portance由于A. Fumigatus奥唑抗性的全球出现，这种机会主义病原体造成严重的健康威胁，因此，它已被列入美国CDC出版物抗生素抗性威胁的钟表名单， 2019年（CDC，2019）。 Azoles在真菌疾病的控制和管理中发挥着关键作用，不仅在临床环境中，还在农业中。因此，唑氏抗性导致有限的治疗库，减少了曲霉病患者的治疗方案，增加了他们的死亡风险。需要证据来了解A. Fumigatus奥唑抵抗是否由于延长使用去甲基酶抑制剂作为杀真菌剂或者是否来自其他地方的杀菌剂，例如临床环境。如果对环境路线进行了说明，则可能会在未来几年中强制使用唑.抗真菌化合物的使用和管理。

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