Species-specific stress adaptation mechanisms drive pathogenicity of Mucorales

Mucormycosis is a devastating, yet poorly understood, human opportunistic disease, causing gross morbidity and over 59,000 deaths worldwide yearly. Initiated by fungal spores of the vast Mucorales order, Mucormycosis results in pleiotropic clinical presentations; species-specific associations with certain host risk factors or geographical locations are well documented. Notably, Rhizopus spp, causing over 70% of Mucormycosis cases globally, show an exceptional ability to withstand abiotic and biotic stress. Moreover, we and others have demonstrated that fungal invasion of human cells, a crucial step for pathogenicity, is reliant on Mucorales stress adaptation capabilities. Thus, we hypothesise that species-specific Mucorales adaptation to natural and in-host environments underpins Mucormycosis pleiotropic pathophysiology. Using our cutting-edge experimental workflows and unrivalled access to clinical and environmental isolates, we will determine how order-wide species-specific Mucorales stress adaptation effects fungal growth and pathogenesis. By identifying the regulatory pathways that mediate species-specific stress adaptation and their conservation across such an heterogenous order, this all-encompassing programme of work will provide a step-change in our understanding of Mucorales biology. Such knowledge will expose therapeutic vulnerabilities to combat this emerging, yet lethal, human fungal disease, driving the development of novel strategies for its clinical management.