Environmental drivers of azole-resistance in Aspergillus fumigatus and its relevance to human health

• Main Author: Shelton, Jennifer May Grace
• Other Authors: Fisher, Matthew
• Format: Doctoral or Postdoctoral Thesis
• Language: unknown
• Published: School of Public Health, Imperial College London 2021
• Subjects: Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10044/1/97977; https://doi.org/10.25560/97977

Aspergillus fumigatus is a fungus that plays an important role in nature and compost production by recycling nutrients from decaying organic matter. The spores are found everywhere – in air and in soil, indoors and outdoors and on every continent except Antarctica - and it is estimated that humans inhale several hundred spores every day. Due to their small size and thermotolerance, A. fumigatus spores are able to enter lung cavities where they can establish and cause infections if not cleared by the innate immune system. It was estimated that in 2011 there were as many as 250,000 individuals in the UK suffering from aspergillosis, with diseases ranging from severe allergic reaction to spore inhalation to invasive infections when spores migrate from the lung into the bloodstream. Aspergillosis is treated with drugs containing azoles, and the proportion of azole-resistant infections in the UK has increased from 3-7% between 1999 and 2001 to 14-20% between 2007 and 2009. Azole-resistant infections result in treatment failure, salvage therapy with more toxic antifungals and decreased patient survival. A. fumigatus acquires azole-resistance in the patient after long-term treatment with azoles but azole-resistant A. fumigatus is also detected in patients who have never been treated with azoles, implying that the infecting spore had acquired resistance before it was inhaled. This is most likely due to adaptation of A. fumigatus in the environment to azoles found in agricultural fungicides with similar structures and modes of action to medical azoles. This thesis seeks to understand the distribution of azole-resistant A. fumigatus in the UK and the environmental factors that may lead to its adaptation through natural selection. To do this, a citizen science approach to sample collection was used; with volunteers in England, Wales, Scotland and Northern Ireland collecting air and soil samples from which A. fumigatus was cultured. Open Access