Improving detection and diagnosis of antimicrobial resistance in Aspergillus fumigatus

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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.