Aspergillus - the Evolution will be Televised
Aspergillius fumigatus is the most important mould pathogen of man. This fungus affects the health of over 20 million people worldwide and is responsible for >350,000 deaths annually. The majority of mortality due to Aspergillus infection is caused by chronic infections that follow tuberculosis, COPD, sarcoidosis or other lung damaging conditions. These infections typically last a period of several years and carry a cumulative year on year mortality of about 8%.
We recently observed that fungi resident in the lung for >5 years had significant changes in their genomes. This adaptation is the end product of an adaptive process that begins with first contact of the fungal spores with the lung epithelium. Specific genome types of A. fumigatus preferentially infect in cases of chronic disease. Phagocytosis and killing of spores are the first steps in compatibility. This is followed by signalling from epithelium to specialised immune cells. Finally, genetic factors in the host play a strong role in receptivity of the host to fungal infection and persistence of the infection.
Fungi that survive this initial interaction, which typically lasts a few hours to days, become resident and begin to establish infections. In CPA these lead to lung cavitation and formation of fungal balls with devastating consequences for the host. Almost all chronic infections become drug resistant – either before or after antifungal treatment as adaptation to the stresses in the lung induces drug resistant phenotypes. Adaptation appears to be driven by large scale genome rearrangements more frequently than by single nucleotide changes.
Understanding features of the A. fumigatus genome that allow survival of early interactions at the lung epithelium and that occur during growth in the lung is critical to our understanding of pathogenicity and may allow targeted diagnostic approaches to identifying at-risk infections.