Whole genome sequencing of BPTI-resistant Saccharomyces cerevisiae
Aprotinin, is an antifibrinolytic that also inhibits fungal growth by limiting magnesium uptake. We investigated the antifungal potential of aprotinin further by assessing the development of resistance using an in vitro model where the model organism S. cerevisiae was serial passaged with Aprotinin. Resistance to Aprotinin developed more quickly than resistance to the plant defensin NaD1 and the clinical antifungal, caspofungin. Genome sequencing of resistant lines linked Aprotinin resistance to deleterious mutations in ptk2 or sky1 genes. Mutations in these genes likely prevent the release of magnesium and other cations from the cell, alleviating the magnesium limitation caused by Aprotinin.