Flipping the switch on fungal pH adaptation

In all human fungal pathogens, adaptations to shifts in pH and salinity are functionally interdependent, essential for causation of human disease, and increasingly encountered in the natural environment due to climate-mediated change and anthropogenic causes. Recent evidence suggests that ecological exposures significantly influence fungal fitness and adaptation, but establishing causality between these exposures and the development of human mycoses remains a major challenge. Viability of fungi in salty, alkaline environments is reliant upon the rapid expression of sodium/potassium efflux ATPases, that are critical for protecting against cation toxicity and maintaining membrane potential across the plasma membrane. However, PacC/Rim signalling – a dominant, broad domain regulator of relevant gene expression - also governs expression of multiple fungal virulence factors (zinc and iron acquisition, secreted proteases, toxins), and is indispensable for infectivity of all human fungal pathogens. Our over-arching hypothesis is that successful adaptation to pH shifts in the natural environment primes opportunistic fungi for infectious growth, reducing barriers to infectivity. Through an innovative combination of evolutionary, molecular, chemical, and structural biology approaches this project will investigate how pH and salinity exposures select for heightened infectivity, particularly in rapidly evolving Aspergillus species.