A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides

Mucormycosis is an emerging fungal infection in immunocompromised patients that can result in patient mortality. Mucormycosis can be caused by Mucor circinelloides, which is also a model organism used to study genetics in the Mucorales. Mucor predominantly grows as hyphae, but inhibition or inactivation of the broadly conserved calcineurin signaling network results in a shift to yeast growth. Here we used whole genome sequencing of 12 calcineurin inhibitor resistant strains and their parent strain to map mutations that conferred bypass of the requirement for calcineurin function in hyphal growth of Mucor.