A One Health approach to combatting AMR in the human pathogen Aspergillus fumigatus.

Infection by Aspergillus fumigatus (Af) causes more deaths globally than any other fungal disease. Over 20 million are affected annually with four million having life threatening invasive and chronic infections with high morbidity and mortality. The azole class of antifungal are first-line therapeutics for treatment of diseases caused by A. fumigatus.

We first demonstrated the emergence of azole resistance in Af in 1991, and since then we and others, have documented a worrying increase in its frequency, both in the clinic and in the wider environment. Working with collaborators across the globe we have developed irrefutable evidence that clinical azole resistance is being driven by the use of similar antifungals used for crop protection.

Our next generation of clinical antifungals (DHODH inhibitors) may provide a solution however just as they are about to be approved for use, novel agricultural fungicides that share their novel mechanism of action have been approved for crop protection purposes. There is now consensus that AMR in Af is an emerging global public health crisis that requires immediate action and the WHO have highlighted Af as a particular concern in its 'global research agenda for AMR in human health'.

To meet this challenge we have developed a transdisciplinary project that will uncover the complex drivers for fungal AMR across one health settings. Working with mycologists, bioinformaticians, evolutionary biologists, clinicians and mathematicians the student will develop a comprehensive understanding of the mechanisms of antifungal drug resistance across one health settings, expand our understanding of why treatment fails in the clinic, develop diagnostics to detect drug resistant strains and develop strategies that may reduce the emergence of resistance and its consequences.