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起着关键作用。然而，A.烟曲霉菌吸入人体后可引起一系列疾病，包括对有某些免疫缺陷的人造成危及生命的感染。我们可以用唑类药物治疗患者，但由于耐药性，这些药物的疗效越来越差。耐药性通常不会在治疗过程中发展，但在感染建立之前已经存在于真菌中。研究人员发现，当这种真菌在含有唑类杀菌剂残留物的有机废物中生长时，它在环境中会产生抗药性。抗药性是由真菌中的DNA变化引起的。当真菌引起感染时，这些需要被检测到，因此可以相应地调整治疗。一个主要的问题是，很难确定病人是否有耐药感染，因为目前的测试不是很好。随着与耐药性相关的DNA变化范围的增加，问题变得更加严重，实际上，对于20%的耐药性真菌，DNA变化是未知的。在这项提案中，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。此外，我们亦会改善一项筛选测试，使其能检测一种重要的新药物的抗药性。更好的诊断测试的发展将使患者受益，将有助于确定患者感染耐药A的频率。烟曲霉，并提高对患者如何感染的理解。