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.

曲霉菌是一种无处不在的模具，它在环境中打破植物材料的作用至关重要。但是，吸入时可能会引起一系列疾病，包括患有某些免疫缺陷的人类的威胁生命的感染。我们可以用硫唑药物治疗患者，但是由于耐药性，这些药物越来越有效。抗药性通常不会在治疗过程中发展，但在建立感染之前已经存在于真菌中。研究人员发现，当真菌在含有硫唑胺残基的有机废物中生长时，这种真菌在环境中变得具有抗药性。电阻是由真菌中的DNA变化引起的。当真菌引起感染时，需要检测到这些，因此可以相应地调整治疗。一个主要的问题是，很难确定患者是否患有抗性感染，因为当前的测试不是很好。与抗药性相关的DNA变化范围的增加，问题恶化了，实际上，对于20％的抗性真菌，DNA变化尚不清楚。在此提案中，我们旨在确认存在现有的DNA变化并找到引起抗性的新DNA变化，然后使用此知识来开发更好的诊断测试。我们还将通过使其能够检测到对重要新开发的药物的耐药性来改善筛查测试。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抗性曲霉的频率，并提高对患者感染方式的理解。