Improving detection and diagnosis of antimicrobial resistance in Aspergillus fumigatus

改进烟曲霉抗菌药物耐药性的检测和诊断

• 批准号: MR/Y034473/1
• 负责人: Paul Dyer
• 金额: $ 46.55万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY034473%2F1
• 关键词: Improving; detection; diagnosis; antimicrobial; resistance

Aspergillus fumigatus is a ubiquitous mould that plays a critical role breaking down plant material in the environment. However, A. fumigatus may cause a range of diseases when inhaled, including life-threatening infections in humans with certain immune defects. We can treat patients with azole drugs, but increasingly these drugs have become less effective due to resistance. Resistance usually does not develop during therapy but is already present in the fungus before infection is established. Researchers have found that the fungus becomes resistant in the environment when it grows in organic waste containing residues of azole fungicides. Resistance is caused by DNA changes in the fungus. These need to be detected when the fungus causes an infection so treatment can be adjusted accordingly. A major problem is that it is very difficult to determine if a patient has a resistant infection because current tests are not very good. The problem is worsened by an increasing range of DNA changes associated with resistance, indeed for 20% of resistant fungi the DNA changes are unknown. In this proposal we aim to confirm the presence of existing DNA changes and find new DNA changes that cause resistance, and then use this knowledge to develop better diagnostic tests. We will also improve a screening test by enabling it to detect resistance against an important newly developed drug. The development of better diagnostic tests will benefit patients, will help establish how often patients are infected with resistant A. fumigatus, and improve understanding of how patients become infected.

烟曲霉是一种普遍存在的霉菌，在分解环境中的植物材料中发挥着关键作用。然而，吸入烟曲霉可能会引起一系列疾病，包括对具有某些免疫缺陷的人类造成危及生命的感染。我们可以用唑类药物治疗患者，但这些药物由于耐药性而变得越来越无效。耐药性通常不会在治疗过程中产生，但在感染发生之前就已经存在于真菌中。研究人员发现，当这种真菌在含有唑类杀菌剂残留的有机废物中生长时，它就会在环境中产生抗药性。耐药性是由真菌 DNA 变化引起的。当真菌引起感染时，需要检测到这些，以便相应地调整治疗。一个主要问题是，由于目前的检测效果不是很好，因此很难确定患者是否患有耐药感染。由于与抗性相关的 DNA 变化范围不断扩大，问题变得更加严重，事实上，对于 20% 的抗性真菌来说，DNA 变化是未知的。在本提案中，我们的目标是确认现有 DNA 变化的存在，并找到导致耐药性的新 DNA 变化，然后利用这些知识开发更好的诊断测试。我们还将改进筛选测试，使其能够检测对重要的新开发药物的耐药性。更好的诊断测试的开发将使患者受益，将有助于确定患者感染耐药烟曲霉的频率，并加深对患者如何感染的了解。