Understanding and mitigating the impact of emerging antifungal resistance (360G-Wellcome-219551_Z_19_Z)

While emerging antimicrobial resistance is widely recognised in bacteria, the emergence of fungi that are resistant to antifungal drugs is underappreciated yet is compromising our ability to treat these serious diseases worldwide. The most widely used class of chemicals, the azoles, are driving the evolution of fungal multidrug resistance through their dual-use in both agricultural and clinical settings. However, we lack critical insights into how these antifungal chemicals are leading to changing patterns of disease in humans. We focus on Aspergillus fumigatus, an environmental fungus to which all humans are exposed causing disease in millions, and which is rapidly evolving resistance to azole antifungal drugs worldwide. Our project aims to understand the risk that azole-resistant aspergillosis presents to public health by identifying the extent to which patients are acquiring resistant infections from environmental sources. We will explore whether the emerging spectrum of mutations that confer drug resistance come with a fitness cost, how these mutations impact upon the global population of A. fumigatus with respect to undesirable phenotypes such as virulence and infectivity. The science that our study produces will be focused on tackling this pandemic in order to retain the efficacy of essential current, and incoming, clinical antifungal drugs.