Highlighted features of quickly evolving and highly resistant strain T1. Mistranslation appears to affect the phosphatidylinositol signal transduction pathways that control several cell cycle events, cell membrane and cell wall remodeling, as well as protein synthesis and turnover, via GCN2, most of which are known to enhance drug resistance. The main features of highly drug-resistant strain T1FH are depicted, i.e., loss of MTLa and the nonsex gene PIKa; phosphatidylinositol signaling and downstream targets such as DNA repair, cell wall remodeling, and mating; GCN2-mediated modulation of protein synthesis; drug efflux pumps; and bud neck formation.